Encoding optical cavity output light

ABSTRACT

Output light from an optical cavity includes, for each of a set of modes, an intensity function. Analyte can be positioned in the cavity, and a mode&#39;s intensity function can be encoded to include information about an optical characteristic of an analyte. For example, the intensity function can include a peak, and its central energy, maximum intensity, contrast, or intermediate intensity width (e.g. FWHM) can indicate the optical characteristic. For example, the information can be about both refractive index and absorption of an analyte.

This application is related to the following co-pending applications,each of which is hereby incorporated by reference in its entirety:“Biosensor Using Microdisk Laser”, U.S. patent application Ser. No.10/930,758, now published as U.S. patent application Publication No.2006/0046312; “Sensing Photon Energies Emanating From Channels or MovingObjects”, U.S. patent application Ser. No. 11/315,992; “ObtainingAnalyte Information”, U.S. patent application Ser. No. 11/316,303;“Position-Based Response to Light”, U.S. patent application Ser. No.11/633,302; “Photosensing Optical Cavity Output Light”, U.S. patentapplication Ser. No. ______ [Attorney Docket No.20051733-US-NP/U1047/034]; “Obtaining Information From Optical CavityOutput Light”, U.S. patent application Ser. No. ______ [Attorney DocketNo. 20060251-US-NP/U1047/035]; “Distinguishing Objects”, U.S. patentapplication Ser. No. ______ [Attorney Docket No.20051733Q1-US-NP/U1047/042]; “Moving Analytes and Photosensors”, U.S.patent application Ser. No. ______ [Attorney Docket No.20051733Q2-US-NP/U1047/043]; and “Implanting Optical Cavity Structures”,U.S. patent application Ser. No. ______ [Attorney Docket No.20060271-US-NP/U1047/036]; “Containing Analyte In Optical CavityStructures”, U.S. patent application Ser. No. ______ [Attorney DocketNo. 20061188-US-NP/U1047/044]; “Tuning Optical Cavities”, U.S. patentapplication Ser. No. ______ [Attorney Docket No.20061409-US-NP/U1047/045]; and “Tuning Optical Cavities”, U.S. patentapplication Ser. No. ______ [Attorney Docket No.20061409Q-US-NP/U1047/046].

BACKGROUND OF THE INVENTION

The present invention relates generally to techniques involving opticalcavities, such as techniques that include information in output lightfrom optical cavities, such as information about analytes.

Liang X. J., Liu, A. Q., Zhang, X. M., Yap, P. H., Ayi, T. C., and Yoon,H. S., “Refractive Index Measurement of Single Living Cell Using aBiophotonic Chip for Cancer Diagnosis Applications,” 9^(th)International Conference on Miniaturized Systems for Chemistry and LifeSciences, Oct. 9-13, 2005, Boston, Mass., 2005, pp. 464-466 describetechniques that perform refractive index (RI) measurement of singleliving cells using a biophotonic chip for cancer diagnosis applications.Liang et al. describe a biophotonic chip that is formed by bonding ametal-coated glass slide with a PDMS slab molded using soft lithographytechnology. An analysis unit embedded in the chip to measure RI includesa laser diode with one surface opposite a gold-coated mirror, forming anexternal laser cavity. A microlens array in the chip improves beamquality, and living cells in a buffer are driven by electrokinetic forceand delivered into an analysis region along microfluidic channels. Adifference in RI between a cell and the buffer changes the effectivecavity length so that laser emission varies, with a wavelength shift.The cell's effective RI can be computed by monitoring wavelength andpower.

Table 1 from Liang shows a number of exemplary refractive indicesrelevant to cancerous cells.

TABLE 1 Cell Type Refractive Index Culture medium 1.350 HeLa 1.392 PC121.395 MDA-MB-231 1.399 MCF-7 1.401 Jurkat 1.390

Liang et al. state that automatic measurement of RI of a living cell inreal time offers low cost, high accuracy disease diagnosis.

It would be advantageous to have improved techniques for opticalcavities, including improved techniques for including information inoptical cavity output light.

SUMMARY OF THE INVENTION

The invention provides various exemplary embodiments, including systems,methods, apparatus, and devices. In general, the embodiments involveencoding information in one or more modes of optical cavity outputlight.

These and other features and advantages of exemplary embodiments of theinvention are described below with reference to the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of a system in which analyte is positionedin an optical cavity and information about the analyte is encoded inoutput light from the cavity.

FIG. 2 is a schematic side view of a homogeneous optical cavity thatcould be used in the system of FIG. 1.

FIG. 3 is a graph showing intensity-energy curves for transmission andreflection from a cavity as in FIG. 2 when operated as a Fabry-Perotcavity, showing ways in which information can be included intransmission mode peaks.

FIG. 4 is a schematic side view of a graded optical cavity that is anexample of an inhomogeneous optical cavity that could be used in thesystem of FIG. 1.

FIG. 5 is a graph showing an intensity-position function of a cavity asin FIG. 4, showing both spectral and harmonic relationships betweenpeaks.

FIG. 6 is a schematic diagram of a setup in which an optical cavity asin FIG. 2 or 4 could operate to provide output light with reflectionmodes.

FIG. 7 is a schematic diagram of an implementation of the system of FIG.1.

FIG. 8 is a schematic circuit diagram of a system implemented as in FIG.7.

FIG. 9 is a flow diagram showing operations of the analyte informationroutine in FIG. 8.

FIG. 10 is a schematic top view of a device that can be used in a systemimplemented as in FIGS. 7 and 8.

FIG. 11 is a schematic cross section of the device of FIG. 10, takenalong the line 11-11.

FIG. 12 is a graph showing two transmission spectra that could beobtained from a device as in FIGS. 10 and 11 with analytes havingdifferent refractive indices.

FIG. 13 includes two graphs showing two transmission spectra that couldbe obtained from a device as in FIGS. 10 and 11 with an analyte absentand present, with the second graph providing an absorption spectrum forthe analyte.

FIG. 14 is a schematic top view of a multiple channel device that can beused in a system implemented as in FIGS. 7 and 8.

FIG. 15 is a schematic cross section of the device of FIG. 14, takenalong the line 15-15.

FIG. 16 is a flowchart showing operations in producing devices as inFIGS. 10, 11, 14, and 15.

FIG. 17 is a schematic top view of components of an implementation of asystem as in FIGS. 7 and 8 in which relative motion occurs between abiochip with an array of analyte-containing wells or locations and aphotosensing array.

FIG. 18 is a schematic diagram of a setup that could be used in animplementation of a system as in FIGS. 7 and 8 in whichanalyte-containing objects such as biological cells pass through a lasercavity.

FIG. 19 is a schematic side view of a graded optical cavity that cancontain analyte and could be used in a system as in FIGS. 7 and 8.

FIG. 20 is a schematic top view of a photosensing component as in FIG.19.

FIG. 21 is a schematic side view of an optical cavity that can be tunedby modifying the length of elastomer spacers and could be used in asystem as in FIGS. 7 and 8.

FIG. 22 is a graph showing two transmission spectra that could beprovided by tuning an optical cavity as in FIG. 21.

FIG. 23 is a schematic diagram of an analyzer on a fluidic structure,where the analyzer includes a system implemented as in FIGS. 7 and 8.

FIG. 24 is a schematic diagram of an implementation of a system as inFIGS. 7 and 8 that can monitor analyte in bodily fluid.

FIG. 25 is a graph showing normalized intensity as a function of photonenergy for a transmission spectrum of an optical cavity with a givenrefractive index and for sensing spectra of several cells of aphotosensing array as in the system of FIGS. 7 and 8 or another system.

FIG. 26 is a graph showing normalized intensity as a function of photonenergy for a transmission spectrum of the same optical cavity as in FIG.25 but with a different given refractive index and for the same sensingspectra as in FIG. 25.

FIG. 27 is a graph showing transmitted intensity as a function of photonenergy with different amounts of absorption as in an optical cavity likethat of FIG. 13.

FIG. 28 is a graph showing transmitted intensity as a function of photonenergy with different amounts of absorption as in FIG. 27, but withtransmitted intensity normalized.

FIG. 29 is a graph showing plotted values of relative change intransmittance as a function of absorption for several reflectivities inan optical cavity filled with air.

FIG. 30 is a graph showing plotted values of an enhancement factor as afunction of absorption for several reflectivities in the same opticalcavity as FIG. 29, again filled with air.

FIG. 31 is a graph showing plotted values of relative change intransmittance as a function of absorption for several reflectivities inthe same optical cavity as FIGS. 29 and 30 but filled with water.

FIG. 32 is a graph showing plotted values of an enhancement factor as inFIG. 30, obtained as a function of absorption for several reflectivitiesin the same optical cavity as FIGS. 29-31, again filled with water.

FIG. 33 is a graph showing intensity as a function of photosensing cellposition for three peaks with the same central energy but differentFWHMs.

DETAILED DESCRIPTION

In the following detailed description, numeric values and ranges areprovided for various aspects of the implementations described. Thesevalues and ranges are to be treated as examples only, and are notintended to limit the scope of the claims. In addition, a number ofmaterials are identified as suitable for various facets of theimplementations. These materials are to be treated as exemplary, and arenot intended to limit the scope of the claims.

“Light” refers herein to electromagnetic radiation of any wavelength orfrequency; unless otherwise indicated, a specific value for lightwavelength or frequency is that of light propagating through vacuum. Theterm “photon” refers herein to a quantum of light, and the term “photonenergy” refers herein to the energy of a photon. Light can be describedas having a “photon energy distribution”, meaning the combination ofphoton energies that are included in the light; highly monochromaticlight, for example, has a photon energy distribution with one peakenergy value. A photon energy distribution can be specified in space andtime: For example, a photon energy distribution can be specified as afunction of position, such as on a surface, or as a function of time; aphoton energy distribution that is “homogeneous” is substantially thesame at all relevant positions, such as the positions of a surface,while a photon energy distribution that is “stable” is substantially thesame at all relevant times.

Light can also be described as provided by a “light source,” which,unless otherwise specified, refers herein to any device, component, orstructure that can provide light of the type described; examples oflight sources relevant to the below-described implementations includevarious kinds of pulsed and unpulsed lasers and laser structures, lightemitting diodes (LEDs), superluminescent LEDs (SLEDs), resonant cavityLEDs, sources of broadband light that is spectrally filtered such aswith a monochromator, and so forth. A “tunable light source” is a lightsource that provides light with a predominant photon energy that can bechanged in response to a signal or operation of some kind.

The term “laser” is used herein to mean any region, element, component,or device in which transitions between energy levels can be stimulatedto cause emission of coherent light, such as in the ultraviolet,visible, or infrared regions of the spectrum. A “laser structure” is anystructure that includes one or more lasers. A “laser cavity” is a regionof a laser in which transitions can be stimulated to cause emission.

To “propagate” light through a region or structure is to transmit orotherwise cause the light to propagate through the region or structure.The light may be referred to as “propagated light” or “propagatinglight”.

Propagating light can often be usefully characterized by direction andspeed of propagation, with direction typically illustrated by one ormore rays and with speed typically being described relative to theconstant c, also referred to as the speed of light in vacuum. Wherelight changes direction in a way that can be illustrated as a vertexbetween an incoming ray and an outgoing ray, the change may be referredto as a “reflection”; similarly, to “reflect” light is to cause thelight to change its direction of propagation approximately at a surface,referred to herein as a “reflection surface”. Where light propagates atless than c, it may be useful to obtain an “optical distance” ofpropagation; for any segment of length d in which speed of propagationis constant ε*c, where ε≦1, optical distance D(ε)=d/ε. An opticaldistance may be referred to herein as an “optical thickness”, such aswhere light is propagating through a thickness of material.

“Photon energy information” refers herein to information about photonenergy, such as information about wavelength, frequency, wavelengthshift, frequency shift, or a distribution of wavelengths or frequencies.“Absolute photon energy information” is information about a given photonenergy value, such as a specific wavelength or frequency, while“relative photon energy information” is information that relates twophoton energy values, whether measured concurrently or at differenttimes.

To “photosense” is to sense photons, and to “photosense quantity” ofphotons is to obtain information indicating a quantity of the photons.Photons that are photosensed are sometimes referred to herein as“incident photons”. A surface at which photosensing occurs is referredto herein as a “photosensitive surface”.

A “photosensor” is used herein to refer generally to any element orcombination of elements that senses photons, whether by photosensingquantity or any other information about the photons. A photosensorcould, for example, provide an electrical signal or other signal thatindicates results of sensing, such as a signal indicating quantity ofincident photons; in general, signals from a photosensor that indicateresults of sensing are referred to herein as “sensing results”. Ifelectrical sensing events occur in a photosensor in response to incidentphotons, the photosensor may integrate or otherwise accumulate theresults of the electrical sensing events during a time period referredto herein as a “sensing period” or “sense period”.

A “range of photon energies” or an “energy range” is a range of energyvalues that photons can have. An energy range can be described, forexample, as a range of wavelengths or a range of frequencies or, inappropriate cases, by the range's central wavelength or frequency andpossibly also the range's width. A “subrange” of a range of photonenergies is a part of the range, and can be similarly described. Acentral wavelength or frequency or other value indicating a centralphoton energy of a range or subrange is sometimes referred to herein asa “central energy”, and may be obtained in various ways, such as byfinding an energy that has maximum intensity or that is another type ofcentral value such as a mean or median of the distribution of lightwithin the range or subrange.

In general, the upper and lower boundaries and widths of ranges andsubranges are approximate. To provide output photons or to photosensequantity of photons “throughout”, “within”, or “in” a range or subrangemeans to provide photons or to obtain information about quantity ofphotons that are predominantly within the range or subrange. In typicalcases, between 60-90% of the provided photons or sensed quantity ofphotons have energies within the range or subrange, but the percentagecould be lower or higher. In some applications, 90% or even 95% or moreof the provided photons or sensed quantity of photons have energieswithin the range or subrange.

Some of the photosensing implementations described herein employstructures with one or more dimensions smaller than 1 mm, and varioustechniques have been proposed for producing such structures. Inparticular, some techniques for producing such structures are referredto as “microfabrication.” Examples of microfabrication include varioustechniques for depositing materials such as growth of epitaxialmaterial, sputter deposition, evaporation techniques, platingtechniques, spin coating, printing, and other such techniques;techniques for patterning materials, such as etching or otherwiseremoving exposed regions of thin films through a photolithographicallypatterned resist layer or other patterned layer; techniques forpolishing, planarizing, or otherwise modifying exposed surfaces ofmaterials; and so forth.

In general, the structures, elements, and components described hereinare supported on a “support structure” or “support surface”, which termsare used herein to mean a structure or a structure's surface that cansupport other structures. More specifically, a support structure couldbe a “substrate”, used herein to mean a support structure on a surfaceof which other structures can be formed or attached by microfabricationor similar processes.

The surface of a substrate or other support surface is treated herein asproviding a directional orientation as follows: A direction away fromthe surface is “up”, “over”, or “above”, while a direction toward thesurface is “down”, “under”, or “below”. The terms “upper” and “top” aretypically applied to structures, components, or surfaces disposed awayfrom the surface, while “lower” or “underlying” are applied tostructures, components, or surfaces disposed toward the surface. Ingeneral, it should be understood that the above directional orientationis arbitrary and only for ease of description, and that a supportstructure or substrate may have any appropriate orientation.

Unless the context indicates otherwise, the terms “circuitry” and“circuit” are used herein to refer to structures in which one or moreelectronic components have sufficient electrical connections to operatetogether or in a related manner. In some instances, an item of circuitrycan include more than one circuit. An item of circuitry that includes a“processor” may sometimes be analyzed into “hardware” and “software”components; in this context, “software” refers to stored or transmitteddata that controls operation of the processor or that is accessed by theprocessor while operating, and “hardware” refers to components thatstore, transmit, and operate on the data. The distinction between“software” and “hardware” is not always clear-cut, however, because somecomponents share characteristics of both; also, a given softwarecomponent can often be replaced by an equivalent hardware componentwithout significantly changing operation of circuitry.

Circuitry can be described based on its operation or othercharacteristics. For example, circuitry that performs control operationsis sometimes referred to herein as “control circuitry” and circuitrythat performs processing operations is sometimes referred to herein as“processing circuitry”.

An “integrated circuit” or “IC” is a structure with electricalcomponents and connections produced by microfabrication or similarprocesses. An IC may, for example, be on or over a substrate on which itwas produced or another suitable support structure. Other componentscould be on the same support structure with an IC, such as discretecomponents produced by other types of processes.

Implementations of ICs described herein include features characterizedas “cells” (or “elements”) and “arrays”, terms that are used withrelated meanings: An “array” is an arrangement of “cells” or “elements”;unless otherwise indicated by the context, such as for a biologicalcell, the words “cell” and “element” are used interchangeably herein tomean a cell or an element of an array. An array may also includecircuitry that connects to electrical components within the cells suchas to select cells or transfer signals to or from cells, and suchcircuitry is sometimes referred to herein as “array circuitry”. Incontrast, the term “peripheral circuitry” is used herein to refer tocircuitry on the same support surface as an array and connected to itsarray circuitry but outside the array. The term “external circuitry” ismore general, including not only peripheral circuitry but also any othercircuitry that is outside a given cell or array.

Some of the implementations below are described in terms of “rows” and“columns”, but these terms are interchangeable. Also, rows and columnsare described herein as examples of “lines”. Within an array, a “line”of cells refers herein to a series of cells through which a line can bedrawn without crossing areas of cells that are not in the line. Forexample, in a two-dimensional array in which cells have uniform areas, aline of cells could be a row, a column, a diagonal, or another type ofstraight line; more generally, a line of cells could be straight orcould include one or more non-straight features, such as curves orangles.

An IC includes a “photosensor array” if the IC includes an array ofcells, and at least some of the cells include respective photosensors. Acell that includes a photosensor may also include “cell circuitry”, suchas circuitry that makes connections with the photosensor, that transferssignals to or from the photosensor, or that performs any other operationother than photosensing. In general, a cell's photosensor and cellcircuitry are within a bounded area of the array, an area sometimesreferred to herein as the “cell's area”. The part of a cell's area inwhich an incident photon can be photosensed is referred to herein as“sensing area”.

In an application of an IC that includes a photosensor array, circuitrythat “responds to” one or more photosensors can be any circuitry that,in operation, receives information from the photosensors about theirphotosensing results through an electrical connection. Circuitry thatresponds to a photosensor could be circuitry in the same cell as thephotosensor, or it could be array circuitry, peripheral circuitry, orother external circuitry, or it could include any suitable combinationof cell circuitry, array circuitry, peripheral circuitry, and otherexternal circuitry. Circuitry that responds to a photosensor couldemploy any suitable technique to read out photosensing results,including, for example, CCD, CMOS, or photodetector array (PDA)techniques.

An IC is or includes a “position-sensitive detector” or “PSD” if itincludes a substantially continuous photosensitive surface and itprovides electrical signals indicating a position resulting from apattern of incident light on the photosensitive surface. For example,the signals could be two currents whose normalized difference isproportional to a centroid of the incident light pattern.

FIG. 1 illustrates general features of system 10, an example of a systemthat can be implemented as described in greater detail below. As withother implementations described below, system 10 involves a combinationof parts or components. As used herein, a “system” is a combination oftwo or more parts or components that can perform an operation together.A system may be characterized by its operation: for example, an “analyteinformation system” is a system that operates somehow on analyteinformation; a “processing system” is a system that performs data orsignal processing; and so forth.

Within a system, components and parts may be referred to in a similarmanner. One component of an analyte information system in whichinformation is obtained about an analyte's optical characteristics, forexample, can be a “detector component” or simply “detector”, meaning acomponent that detects light; similarly, a “light source component”includes one or more light sources; an “optical component” performs anoptical operation; a “photosensing component” performs a photosensingoperation; a “light-transmissive component” or simply “transmissioncomponent” transmits light; a “light-reflective component” or simply“reflective component” reflects light; an “analyte positioningcomponent” operates to transfer analyte through a series of positions;an “optical cavity operating component” provides optical cavityoperations; and other examples are defined further below. Other parts orcomponents can be characterized by their structure.

System 10 includes analyte positioning component 12 and optical cavityoperating component 14. Exemplary operations of analyte positioningcomponent 12 are illustrated in boxes 26, 28, 30, 32, 34, and 36, andeach exemplary operation involves positioning analyte in a respectiveoptical cavity; each optical cavity illustratively includeslight-reflective components 40 and 42. Between light-reflectivecomponents 40 and 42 is a light-transmissive region, in at least part ofwhich an analyte is positioned during the illustrated operation. In eachexample, there could be additional similar parts or components (notshown) that prevent analyte from flowing out or otherwise moving out ofthe cavity in directions perpendicular to the plane of the illustration.

The term “reflective optical cavity”, or simply “optical cavity” or“cavity”, refers herein to a light-transmissive region that is at leastpartially bounded by light-reflective components, with thelight-reflective components and the light-transmissive region havingcharacteristics such that a measurable portion of light within thelight-transmissive region is reflected more than once across thelight-transmissive region. An “optical cavity component” is a componentthat includes one or more optical cavities.

Within the broad category of optical cavities, there are various morespecific types: For example, a laser cavity, mentioned above, is anexample of an “emitting optical cavity” or simply “emitting cavity” thatcan operate as a source of emitted output light even when it is notreceiving input light from an external light source, with the emittedlight ordinarily resulting from a gain medium within thelight-transmissive region; similarly, a “transmissive cavity” canoperate, in response to input light from one or more external lightsources at an entry surface, providing a transmitted portion of itsoutput light at an exit surface different than the entry surface (acomplementary, reflected portion may be provided at the entry surface);a “Fabry-Perot cavity” is a reflective optical cavity in whichconstructive interference (or positive reinforcement) occurs in one ormore photon energy subranges while destructive interference occurs inothers.

The various exemplary implementations described below address problemsthat arise in obtaining information about analytes using opticalcavities. The implementations are especially relevant to optical cavityoutput light that includes information about an optical characteristicof an analyte. One problem is the difficulty of obtaining highresolution information about optical characteristics rapidly and withoutbulky, expensive equipment; absorption spectroscopy of analytes influid, for example, typically requires wavelength resolution 1-10 nm orbetter. This can not be achieved with simple filter-based opticalsystems; instead, bulky spectrometers are necessary. Another problem inabsorption spectroscopy is that a long interaction length between lightand analyte is required to detect small absorption changes, so thatlarge sample chambers are necessary, which require a large amount ofanalyte. Another problem is that accurate information may be difficultto include in output light because of various types of noise that may bepresent in an optical system. Yet another problem is that techniquesused to include information about one optical characteristic are usuallynot adapted for another characteristic, so that several differenttechniques must be used to include information about several opticalcharacteristics in an optical cavity's output light, e.g. toconcurrently include information on refractive index and absorptionproperties.

A Fabry-Perot cavity or other optical cavity that can operate to provideoutput light in one or more photon energy subranges while not providingoutput light with other photon energies may be described as having oneor more “modes”, each for a respective one of the output light energysubranges; if the cavity is a transmissive cavity, modes of itstransmitted output light may be referred to as “transmission modes” andmodes of its reflected output light may be referred to as “reflectionmodes”. In the reflection spectrum, either the valley-like dips or theplateau-like reflection bands between the dips can be considered as“reflection modes”. An emitting cavity can be described as “stimulatedat” a mode by any operation that results in emission of output light inthe mode's photon energy subrange. Similarly, a transmissive cavity canbe described as “illuminated at” a mode by any operation that providesinput light that results in transmission or reflection of output lightin the mode's photon energy subrange.

In typical implementations of optical cavities, two light-reflectivecomponents have approximately parallel reflection surfaces and thelight-transmissive region is sufficiently uniform that measurementswould indicate many reflections of light within the light-transmissiveregion. Such cavities define a directional orientation as follows:Directions in which light could propagate and be reflected many timeswithin the light-transmissive region are referred to herein as“reflection directions”, and generally include a range of directionsthat are approximately perpendicular to both reflection surfaces.Directions that are approximately parallel to both reflection surfaces,on the other hand, are generally referred to herein as “lateraldirections”. In addition, the terms “in”, “inward”, or “internal”generally refer to positions, directions, and other items within ortoward the light-transmissive region between the reflection surfaces,while “out”, “outward”, and “external” refer to positions, directions,and other items outside or away from the light-transmissive region. Ingeneral, it should be understood that the above directional orientationis arbitrary and only for ease of description, and that an opticalcavity may have any appropriate orientation.

The above directional orientation does not in general apply to angle ofincidence of input light. Transmissive cavities can typically operate inresponse to incident light that is not perpendicular to entry surfacesor reflection surfaces. Light incident on a transmissive cavity's entrysurface at any angle is reflected multiple times within the cavity,producing transmission modes in accordance with the cavity's geometry.But transmission modes are affected by angle of incidence: Depending onthe type of cavity and the angle of incidence, modes can be blue shiftedor red shifted in comparison to perpendicular incidence; if all lightenters a cavity at approximately the same angle, performance is affectedonly by the shifting of modes and modes are not also broadened, butperformance is reduced if a cavity receives incident light distributedacross a large angular range because transmission mode structure is thenaveraged over multiple angles.

Analyte is “present in”, “positioned in”, “contained in”, or simply “in”an optical cavity when the analyte is in all or some part of thecavity's light-transmissive region. An optical cavity provides“analyte-affected output light” if the optical cavity's output light isdifferent in some way when analyte is present in the cavity than whenanalyte is absent, with the difference being due to the analyte'soptical characteristics.

More generally, a cavity “includes a region” if the region is all orsome part of the cavity's light-transmissive region. A region has a“changeable optical characteristic” if the region as a whole can becharacterized as having the same value for the optical characteristicand if the value varies as a function of time; for example, a region hasa “changeable optical absorption characteristic” if the region can becharacterized by a single value for optical absorption and if that valuefluctuates or otherwise varies over time. One way in which a region of acavity can have a changeable optical characteristic is for the region tocontain, in succession, a series of different analytes that havedifferent optical characteristics affecting the cavity's output light,but there are many other possible ways in which a region could have achangeable optical characteristic with or without change in itscontents.

In box 26 in FIG. 1, wall-like part 44 closes one end of thelight-transmissive region between components 40 and 42, preventing fluidfrom flowing out of the cavity. Therefore, analyte 46 can enter thecavity as indicated by arrow 48 and can be held there by additionalwalls (not shown) at either side of the cavity. In effect, analyte 46 isheld as if it were in a cup as a result of this operation. The flow ofanalyte could take any appropriate form, however, including flow underpressure, flow in response to gravity, flow as a result of capillaryaction, drift of analyte, or diffusion of analyte.

Box 28 illustrates a similar operation in which a block-like component50 has a well-like opening defined in a surface, which can be filled byanalyte 52 as indicated by arrow 54. Analyte 52 could move into thewell-like opening by any of the processes described above in relation tobox 26. After analyte 52 is in position, light-reflective component 40is placed over component 50 to form an optical cavity. Light-reflectivecomponent 42 could be positioned below component 50 throughout theoperation or the operation could include positioning light-reflectivecomponent 42 under component 50. This type of operation could beperformed, for example, to position analyte in the wells of a biochip orother analytic tool with an array of well-like openings.

In Box 30, analyte 60 flows through the optical cavity betweencomponents 40 and 42 as indicated by arrows 62. This technique could beused with fluid analytes such as liquid, gas, or aerosols, or withfluid-borne analytes dissolved, suspended, or otherwise carried by afluid. In addition, this positioning technique could be used withfloating particulate analytes in a vacuum or plasma. In general, theoperation could be performed in any of the ways described above inrelation to box 26, and a duct or other channel could be employed tocontrol flow of analyte although, in some implementations, the opticalcavity could be completely open in lateral directions, allowing analyteto enter and exit in any lateral direction.

The positioning operation in box 32 is similar to that in box 30, butwith fluid 66 carrying objects 68 and 70 through the cavity in a lateraldirection as indicated by arrows 72. Similarly, in box 34, medium 74 isinside the cavity, and objects 76 and 78 are moving through medium 74and therefore through the cavity, as indicated for each object by itsrespective arrow; as suggested by the lengths of the arrows, objects 76and 78 could move at different rates, and it is also possible that theycould move in different directions, possibly including non-lateraldirections.

Examples of objects that could occur in implementations as describedherein include droplets, bubbles, small volumes of fluid, singlemolecules, agglomerated molecules, molecule clusters, biological cells,viruses, bacteria, proteins, DNA, microparticles, nanoparticles, andemulsions. A droplet or small volume of fluid may, for example, includeatoms, molecules or other particles that affect refractive index,absorption, or other optical characteristics. An object “travels” or iscaused “to travel” if the object moves through a succession ofpositions. For example, the object could be conveyed in a fluid, such asa liquid, gas, or aerosol, in which case the object may be referred toas being “carried by the fluid.”

The term “path” is used herein to refer to a substantially continuousseries of positions through which an object may travel. A path is“through a cavity” if an object following the path passes through partof the cavity. A photosensing component, such as an array or PSD, is“positioned along” or “along” a path through a cavity if the componentis positioned near the cavity in such a way that, when an objectfollowing the path affects output light from the cavity, thephotosensing component can obtain sensing results that includeinformation about how the object is affecting the output light. Anobject following a path in such a case can be said to move “past thearray”.

The positioning technique illustrated in box 36 resembles in some waysthe technique in box 26, but the presence of analyte in the cavity canhave a specific effect that is different. As shown at left in box 36,the optical cavity is “asymmetric” in the sense that the reflectivity oflight-reflective components 40 and 42 is not the same when the cup-likeopening in the cavity does not contain analyte. As shown at left in box36, however, analyte, illustratively fluid 84, can be positioned in theopening, such as in any of the ways described in relation to box 26,above: In this configuration, because of the presence of fluid 84, theoptical cavity is “symmetric” in the sense it can operate as if thereflectivities were equal, as described in greater detail below inrelation to reflection modes of a Fabry-Perot cavity.

After or during positioning by component 12 in any of the ways describedabove, during a time when analyte is in cavity 20, optical cavityoperating component 14 can cause the cavity to provide output lightencoded with information about one or more optical characteristics ofthe analyte. As used herein, to “encode” output light with informationmeans to modify one or more features of the output light in accordancewith the information so that the information can, at least in principle,be again obtained from the output light, such as by detecting,measuring, or otherwise sensing the modification. Output light that ismodified in this way is sometimes referred to herein as including“encoded information” or as “encoding information” or simply as“encoded”.

The graph in box 88 illustrates ways in which output light can encodeinformation. As shown, component 14 can control illumination orstimulation of cavity 20 so that it provides light in one or more modes,such as transmission modes or reflection modes. The graph shows an“intensity function” for first, second, and third modes, meaning thatoutput light from each mode can be represented as a function, such as ofphoton energy or, in some implementations, of position. The intensityfunction of at least one of the modes can be modified as a result of ananalyte's presence to encode information about one or more opticalcharacteristics of the analyte, providing analyte-affected output lightthat includes encoded information about the analyte's opticalcharacteristics, such as about a value or a change in value of anoptical characteristic, in which case the intensity function may bedescribed as “analyte-encoded” herein.

An intensity function can have any of a wide variety of shapes andfeatures, but a shape that frequently arises in transmission modes isthe “peak”, a shape characterized by a maximum value from which a curvefor the function slopes steeply downward. Peaks have various features,including “central value”, meaning the value of the other parameter atwhich the peak's maximum occurs, such as “central energy” for anintensity-energy function; “maximum intensity” or simply “maximum” or“amplitude”, meaning the intensity value at the peak's maximum, whethermeasured as an absolute intensity or relative to another feature, suchas a nearby minimum value; “contrast”, meaning a value indicatingrelationship between magnitudes of the peak's maximum intensity and ofone or more nearby minima of the transmission intensity function; and“intermediate intensity width”, meaning the width of the peak at anintensity somewhere between its maximum and nearby minima, such as afull width half maximum (FWHM). In general, information encoded in oneof these features can be recovered in various ways, including thosedescribed in co-pending U.S. patent application Ser. No. ______,[Attorney Docket No. 20060251-US-NP/U1047/035], entitled “ObtainingInformation From Optical Cavity Output Light” and incorporated herein byreference in its entirety.

In the graph in box 88, solid-line curve 90 in the graph illustrates theintensity functions of first, send, and third modes withoutanalyte-encoding; as can be seen, each intensity function has a centralenergy, an amplitude, a contrast, and an FWHM, and information can beencoded by modifying any of these or other features of an intensityfunction. In the illustrated example, dashed-line curve 92 has beenencoded by changing at least one of central energy, amplitude, contrast,and FWHM for each of the three modes. Central energies of the intensityfunctions for the first, second, and third modes have been shifted fromcurve 90 to curve 92, such as by a change in refractive index.Similarly, amplitudes, contrasts, and FWHMs of the intensity functionsof the second and third modes are changed from curve 90 to curve 92,such as by changes in absorption spectrum.

Analyte-encoded output light from modes of an optical cavity, providedby component 14, could be used in a variety of ways. For example, asdescribed in greater detail below, it could be provided to one or morephotosensitive surfaces of photosensing components, and some or all ofthe encoded information could be obtained and used by other components,inside or outside of system 10. Alternatively, if provided in a visiblerange, the output light could be viewed to obtain some of all of theencoded information.

The general features in FIG. 1 could be implemented in many ways, asexemplified by the various implementations described below. Inparticular, the exemplary implementations below include examples of howanalytes could be positioned in optical cavities in various ways beforeor during analyte-encoding of output light; in particular, variousstructures within optical cavities could operate or cooperate toposition analyte. The exemplary implementations also include variousexamples of optical cavity operation that performs analyte-encoding ofvarious kinds.

Many different types of mirrors and other light-reflective componentscould be used in an optical cavity device, some of which are describedbelow. Similarly, light-transmissive regions of optical cavities couldbe implemented in many different ways, some of which are describedbelow; for example, elastomer or other deformable material might fillpart of a light-transmissive region, and elastomer or other deformablematerial could in general be used to implement an optical cavity withtransmission modes.

FIG. 2 illustrates optical cavity 100, an example of a “homogeneousoptical cavity”, meaning a cavity whose light-transmissive regionincludes an extended part with substantially constant optical distance Dbetween its reflection surfaces, sometimes referred to as its“homogeneous region”. The homogeneous region of cavity 100illustratively includes substantially all of light-transmissive region102 where it is between and partially bounded by light-reflectivecomponents 104 and 106, though partially and completely boundedhomogeneous regions with various other shapes and arrangements arepossible.

Inward-facing surfaces 110 and 112 of components 104 and 106,respectively, can be implemented, for example, as mirrors or otherreflective components that closely approximate the reflection surfacesof cavity 100. The characteristics of components 104 and 106 and of anymaterial or structure within region 102 are such that a measurementwould indicate that at least a portion of light within region 102 isreflected more than once. A reflection direction in which light can berepeatedly reflected between the reflection surfaces is represented bybidirectional ray 114, while one of the possible lateral directions inan x-y plane approximately perpendicular to ray 114 is illustrated by anx-axis at the lower right.

FIG. 2 also illustrates two ways in which homogeneous optical cavitiescan operate to provide output light, represented schematically by arrows116. In both operations, output light can be provided at an exitsurface, illustratively outward-facing surface 120 of component 106,which may or may not be approximately parallel to the reflectionsurfaces.

In the first operation, optical cavity 100 operates as an emittingcavity, such as a laser cavity. Typically, an emitting cavity operatesin response to stimulation of some type, represented schematically inFIG. 2 by stimulation arrow 122. Stimulation arrow 122 could, forexample, represent electrical or optical stimulation.

In the second operation, optical cavity 100 operates as a transmissivecavity, such as a Fabry-Perot interferometer. A transmissive cavityoperates in response to input light from one or more external lightsources, represented in FIG. 2 by illumination arrows 124. Input lightcan be received at an entry surface, illustratively outward-facingsurface 126 of component 104, which also may or may not be approximatelyparallel to the reflection surfaces. As noted above, a reflected portionof output light can be provided at the entry surface, as described ingreater detail below.

FIG. 3 is an intensity-energy graph or “output spectrum” for opticalcavity 100 when operated as a Fabry-Perot cavity such as aninterferometer. Since photon energy is inversely proportional towavelength, wavelength increases as one moves leftward along thehorizontal axis, while the inverse of the wavelength (1/λ) increases asone moves rightward, as suggested by the labeling of points on thehorizontal axis; it follows that energy and frequency would alsoincrease to the right.

The graph in FIG. 3 includes a solid-line curve with peaks 130, 132, and134, each of which is an “intensity-energy peak” or simply “intensitypeak” that results from a respective transmission mode of cavity 100,illustratively the Kth, (K−1)th, and (K−2)th modes, and has an amplitudeImax, which could result from broadband illumination in the photonenergy subranges of all the modes shown; such a curve is sometimesreferred to herein as a “transmission spectrum”. FIG. 3 also includespart of dashed-line curve 136 that is the complement of the transmissionspectrum, i.e. the intensity-energy curve for light that is reflectedrather than transmitted by optical cavity 100; such a curve is sometimesreferred to herein as a “reflection spectrum” and its reflection modesare broad and separated by narrow valleys rather than being narrow peaksseparated by broad valleys like the transmission modes. The term “outputmodes” is sometimes used herein as a generic term that encompassestransmission modes and reflection modes.

The maxima of intensity-energy peaks 130, 132, and 134 (and thecomplementary minima between reflection bands) are spaced apart as afunction of photon energy (illustratively wavelength), and thedifference between the central energy of adjacent transmission modepeaks is referred to as “free spectral range” or “FSR”. FSR can betreated as the bandwidth over which adjacent intensity-energy peaks donot overlap, while the full width half maximum (FWHM) of the peaks canbe treated as the minimum resolvable bandwidth. FSR, FWHM, and theirratio are all sometimes treated as figures of merit in designing aFabry-Perot cavity.

The wavelength λ of each intensity-energy peak can be obtained from theequation λ(k)=2nD/k, where n is the refractive index of the cavity and kis a non-zero integer. Therefore, if refractive index of the cavitychanges, λ(k) also changes for a given value of k, so that if a peak'scentral energy changes, as indicated by Δλ+ and Δλ− for peak 134, thechange provides information about refractive index change. Similarly,the intensity of the peaks depends on absorption in the cavity, so thatif the intensity of a peak departs from Imax, as indicated by ΔI+ andΔI− for peak 134, the change provides information about absorptionchange.

FIG. 4 illustrates graded optical cavity 150, an example of an“inhomogeneous optical cavity”, meaning a cavity that does not meet theabove definition of a homogeneous optical cavity. Because of thesimilarities between cavities 150 and 100, parts and components ofcavity 150 that are substantially the same as those in FIG. 2 arelabeled with the same reference numbers. In cavity 150, however, region152 is not homogeneous, but rather has “laterally varying opticaldistance” between reflective surfaces, meaning that the optical distancevaries in one or more lateral directions; in the illustrated example,the optical distance illustratively increases linearly from D(0) at oneend of cavity 150 (x=0) to D(Xmax) at the opposite end (x=Xmax), butoptical distance between reflective surfaces in an inhomogeneous opticalcavity could vary laterally in any appropriate way, and need not varymonotonically, linearly, or with any other type of uniformity.

Because of its linearly varying optical distance or thickness, cavity150 can operate as a linearly variable optical filter (LVF), a type oftransmissive cavity. This capability is illustrated by the functionT(x), a “laterally varying energy output function”, meaning that photonenergies of output light depend on lateral position; in this case, thefunction relates output photon energy (in response to input lightrepresented by illumination arrows 124) to lateral position on exitsurface 120. For an LVF, the simple relationship λ(x)=T(x)=d′x+λ(0) canhold, where d′ is a constant that depends on gradient of opticalthickness and can be graphically represented by the constant slope(λ(X2)−λ(X1))/(X2−X1)) of position-wavelength graph 154 at right in FIG.4.

In general, the characteristics of output light at each position onsurface 120 can be a function of parameters other than opticalthickness, including, for example, photon energy and incident directionof input light 124 received at counterpart positions on surface 126. Inparticular, the output light may depend on whether the input light isnarrow band, broad band, or multi-modal, as can result from a set oftransmission or reflection modes. Narrow band or multi-modalillumination of an LVF, for example, can produce one or several outputlight spots, respectively.

The graphs at right in FIG. 4 also illustrate intensity-energy peaks 160and 162 that would result if cavity 150 were illuminated by narrow bandinput light with central energy of λ(X1) and λ(X2), respectively, and,in response, operated as an LVF as described above. At position X1, forexample, T(X1) results in transmission of output light represented byarrow 164, within a photon energy subrange characterized by centralenergy λ(X1); at position X2, T(X2) results in transmission of outputlight represented by arrow 166, within a photon energy subrangecharacterized by central energy λ(X2); for the illustrated laterallyvarying energy output function, if X1≠X2 and the difference between X2and X1 is sufficient, then T(X1)≠T(X2), and λ(X1)≠λ(X2). On the otherhand, for relatively small regions of output surface 120, cavity 150might in some cases operate locally as a homogeneous cavity withtransmission modes as illustrated in FIG. 3. It follows that parametersapplicable to transmission modes are sometimes also useful forintensity-energy peaks from inhomogeneous cavities; in particular,information about changes in refractive index and absorption cansometimes be provided through changes in intensity-energy peaks in waysshown in FIG. 3.

Various techniques can be used to operate optical cavities to produce“laterally varying photon energy distributions” or simply “laterallyvarying energy distributions”, meaning distributions in which photonenergy of light varies as a function of lateral position. Suchdistributions can be produced, for example, with inhomogeneous opticalcavities having laterally varying optical thicknesses and, even withhomogeneous optical cavities, with angled illumination from a pointlight source rather than perpendicular illumination; several possibletechniques are described in co-pending U.S. patent application Ser. No.11/316,438, entitled “Photosensing Throughout Energy Range and inSubranges” and incorporated herein by reference in its entirety.

More generally, an inhomogeneous optical cavity can have any appropriatelaterally varying energy output function, including functions that arenonlinear or nonuniform in other ways. Some of the below-describedimplementations, for example, involve functions that are affected bypresence of an analyte in an optical cavity. As with homogeneouscavities, an inhomogeneous cavity's light-transmissive region can becompletely between and partially bounded by light-reflective componentsas in FIG. 4, but partially and completely bounded light-transmissiveregions with various other shapes and arrangements are possible.

FIG. 5 is an intensity-position graph for optical cavity 150 whenoperated as a Fabry-Perot cavity such as an interferometer. FIG. 5 issimilar to FIG. 3, and the peaks illustratively have maximum amplitudeImax as in FIG. 3 and their central energies and amplitudes (and FWHMs)could be affected as shown for peak 134 in FIG. 3; but the x-axis inFIG. 5 represents position in the x-direction in FIG. 4 rather thanphoton energy.

In the example shown in FIG. 5, cavity 150 is illuminated at P(P≧2)photon energies ranging from λmin to λmax, resulting in a series ofoutput modes (illustratively transmission modes) for each photon energyλ(p) of illumination at those positions on the x-axis where thecondition λ(p)=2n*D(x)/k is satisfied for integer values of k. The firsttransmission mode shown for λmin is peak 170 at x=Xmin(1) and for λmaxis peak 172 at x=Xmax(1). The second transmission mode shown for λmin ispeak 174 at x=Xmin(2) and for λmax is peak 176 at x=Xmax(2). The thirdtransmission mode shown for λmin is peak 178 at x=Xmin(3), and so forth.

In the example of FIG. 5, transmission modes are sufficiently separatedalong the x-axis to prevent interference between adjacent transmissionmodes. As can be seen, Xmin(2) is sufficiently greater than Xmax(1) thatpeaks 172 and 174 do not interfere, and Xmin(3) is similarlysufficiently greater than Xmax(2) that peaks 176 and 178 do notinterfere. If instead the first transmission mode of λmax were peak 180due to an increase from Xmax(1) to Xmax(error), as indicated by arrow182, interference between peaks 180 and 174 would begin to occur; as thefirst transmission mode of λmax increased further, loss of informationwould occur due to ambiguity between peak 180 and peak 174. Problems ofthis type can be avoided by coordination of photon energy range withcavity parameters; for example, cavity thickness D can be sufficientlysmall that only one output mode occurs over the range from λmin to λmax.The free spatial range (FSR) between the modes in a particularwavelength range can also be increased by reducing the tilt of theinhomogeneous (graded) cavity.

FIG. 6 shows a setup in which optical cavity structure 190 receivesinput light represented by arrows 192 through beam splitter 194. Opticalcavity structure 190 can include a transmissive cavity implemented as inany of the ways described in relation to FIGS. 2-5 or in any othersuitable way. In response to the input light, the cavity provides atransmitted portion of output light represented by arrows 196 and areflected portion of output light represented by arrows 198. The use ofbeam splitter 194 is merely illustrative of ways in which input lightand reflected light could be separated; for example, input light couldbe incident upon an entry surface at a sufficiently large angle from thenormal that reflected light is separated from input light, though thenon-perpendicular angle of incidence reduces performance of the opticalcavity.

As suggested above in relation to FIG. 3, refractive index changes inthe optical cavity will cause the same shift in both transmitted andreflected modes, while absorption in the optical cavity will similarlycause decreased amplitude and contrast and increased FWHM in bothportions, with the effect of absorption typically varying as a functionof photon energy; a curve showing absorption as a function of photonenergy is sometimes referred to herein as an “absorption spectrum”.

FIG. 7 shows system 200, an exemplary implementation of system 100 inFIG. 1. System 200 includes optical cavity structure 202, a structurethat can include one or more optical cavities with features describedabove. In system 200, at least one of the optical cavities in structure202, represented schematically by cavity 204, can contain an analyte,illustratively being provided to cavity 204. The presence of analyte incavity 204 affects the output light provided by structure 202, and theanalyte-affected output light, represented by arrow 206, can then bephotosensed within detector 210. For example, detector 210 may include aphotosensing component with one or more photosensitive surfaces at whichlateral variation of light is detected, such as after the light passesthrough an LVF. The sensing results from detector 210 can be provided toother components within system 200 or to external components, asrepresented by arrow 212.

Detector 210 could be implemented in many different ways, such as with aphotosensing IC, as described in co-pending U.S. patent application Ser.No. ______ [Attorney Docket No. 20051733-US-NP/U1047/034], entitled“Photosensing Optical Cavity Output Light” and incorporated by referenceherein in its entirety. The implementation in FIG. 7 might, however,alternatively be implemented with photosensing components that do notinclude photosensing ICs, such as with one or more discrete photodiodes.

Although cavity 204 can be any suitable type of homogeneous orinhomogeneous optical cavity, including an emitting cavity or atransmissive cavity, FIG. 7 illustratively shows one or more lightsources 220 that can be included within system 200 to illuminate one ormore optical cavities. As represented by arrow 222, structure 202receives input light from light sources 220. If optical cavity 204 isilluminated as shown, the analyte-affected output light represented byarrow 206 could include one or both of transmitted and reflected light.

FIG. 8 illustrates electrical components that can be used inimplementing system 200 as in FIG. 7. System 200 illustratively includescentral processing unit (CPU) 240 connected to various componentsthrough bus 242, but a wide variety of other architectures could beemployed, including any appropriate combination of hardware andsoftware, as well as specialized hardware components such as applicationspecific integrated circuits (ASICs) for one or more of the illustratedcomponents or in place of a software component executed by CPU 240.

System 200 also includes component input/output (I/O) component 244,memory 246, integrated circuit input/output (IC I/O) 248, and externalI/O 249, all connected to bus 242. System 200 can include various othercomponents (not shown) connected to bus 242. In addition to connectionsthrough external I/O 249 by which signals can be provided to andreceived from external devices, bus 242 can also be connected directlyto components outside of system 200.

Component I/O 244 permits CPU 240 to communicate with certain componentsof system 200, illustratively including illumination control 250, cavitycontrol 252, and analyte control 254. For interactive applications,component I/O 244 could also be connected to a suitable user interface,such as a monitor and keyboard (not shown). In the exemplaryimplementation in FIG. 7, illumination control 250 can include lightsources 220 (FIG. 7) and circuitry for controlling them; cavity control252 can include electrodes or other components that can be operated tocontrol cavity 204 and other cavities and can also include circuitryconnected to those components; and analyte control 254 can similarlyinclude fluidic devices or other components that can operate to transferanalyte into, through, or out of cavity 204 or other cavities or toproduce relative movement between analyte and an array or a cavity, andcan also include circuitry connected to those devices and components.

In the illustrated implementation of system 200, IC I/O 248 is a similarI/O component that permits CPU 240 to communicate with one or more ICs,such as in detector 210 in FIG. 5. M ICs are illustrated by a seriesfrom IC(O) 260 to IC(M−1) 262, including IC(m) 264 with a photosensorarray 266.

Memory 246 illustratively includes program memory 270 and data memory272, although instructions for execution by CPU 240 and data accessduring execution of instructions could be provided in any suitable way,including through external devices or components. The routines stored inprogram memory 270 illustratively include analyte information routine274. In addition, program memory 270 could store various additionalroutines and also subroutines (not shown) that CPU 240 could call inexecuting routine 274. Similarly, the data in data memory 272illustratively include calibration data 276, but could include variousadditional items of data and data structures accessed by CPU 240.

In executing routine 274, CPU 240 can provide signals to cavity control252 and to analyte control 254 so that an analyte is present in cavity204, for example, with the analyte having optical characteristics thataffect output light from cavity 204. CPU 240 can also provide signals toillumination control 250 so that cavity 204 is appropriately illuminatedto provide analyte-affected output light. CPU 240 can also providesignals to each of ICs 260 through 262 to obtain sensing results thatinclude information about the analyte in cavity 204. In animplementation with a position-sensitive detector (PSD), CPU 240 couldinstead provide whatever signals are necessary to obtain photosensedquantities from the PSD; for example, CPU 240 could control circuitry toconnect output currents from the PSD to a differential amplifier.

FIG. 9 illustrates one example of how analyte information routine 274could be implemented in a system like system 200 in FIGS. 7 and 8. Theroutine in FIG. 9 could be implemented with a variety of analytepositioning operations, such as with single objects moving along pathsthrough cavities past arrays; with spaced multiple objects moving alongpaths through cavities past arrays; or with continuous streams ofobjects, such as small volumes of fluid, moving along paths throughcavities past arrays, in each case subject to appropriate constraints.

The routine in FIG. 9 follows a general strategy of performing a seriesof readout operations, after which information is combined and provided.It would also be possible to provide the information from each readoutoperation immediately or to provide information both immediately aftereach readout operation and also after a series of readout operations.

When CPU 240 executes the operation in box 300, it performs apre-sensing readout. The purpose is to obtain information necessary tolater perform a sensing readout. The information could be obtained inthe ways described in co-pending U.S. patent application Ser. No.11/315,992, entitled “Sensing Photons from Objects in Channels” andincorporated herein by reference in its entirety.

Using the information from box 300, CPU 240 could obtain informationabout each object and determine an appropriate sensing period for eachobject, in the operation in box 302. For example, CPU 240 could performcalculations to determine whether one or more objects are present, theposition of each object, and the speed of each object. Using thisinformation and taking into account previously calculated sensingperiods for the same objects, if any, CPU 240 can also determine anappropriate sensing period to be used during sensing readout; ingeneral, the sensing period must provide an integration time shorterthan the time necessary for an object to pass each cell in an array.Each object can therefore have a unique sensing period.

The operation in box 302 can also include providing any necessarysignals through component I/O 244 to adjust movement of objects, such asby adjusting fluid speed; to adjust illumination or stimulation of theoptical cavity; or to adjust characteristics of the optical cavity, suchas by adjusting optical distances between light-reflective components orby adjusting temperature or another operating parameter of the cavity.These signals could include any appropriate combination of signals toillumination control 250, cavity control 252, and analyte control 254,two or more of which could be concurrently receive signals so that morethan one adjustment is made at the same time, such as system temperatureand also illumination. CPU 240 could provide such signals based in parton information it obtains from optical cavity output light. In adjustingmovement of objects, however, CPU 240 would operate as an analytepositioning component, as described above in relation to FIG. 1, whileit would operate as an optical cavity operating component in adjustingillumination or stimulation of the optical cavity or in adjustingcharacteristics of the optical cavity.

CPU 240 can then cause operation of the cavity in a way that encodesinformation about the analyte's optical characteristics and can alsoperform sensing readout on the cavity's output light, in box 304. Thisoperation includes providing any further signals through component I/O244 so that the cavity provides analyte-encoded output light and alsoproviding signals through IC I/O 248 so that photons are photosensedcumulatively during the sensing period obtained in box 302. During thisoperation, CPU 240 may also provide signals to peripheral circuitry onan IC so that analog quantities photosensed by cells are adjusted basedon reference values. After adjustment, if any, analog quantities can beconverted to digital signals for readout. The operation in box 304 canbe implemented in whatever manner is appropriate for a givenphotosensing IC, whether a CCD or CMOS implementation, and regardless ofwhether readout is purely serial or is also parallel.

Since an analyte's or object's optical characteristics can affect theoutput light provided from a mode of an optical cavity, such as in theways described above in relation to FIGS. 1, 3, and 5, information aboutthe optical characteristics is present in the cavity's output light,encoded in intensity functions of one or more modes. Sensing resultsobtained in box 304 can therefore include part or all of the encodedinformation. Detector 210 as in FIG. 7 can include, for example, alaterally varying transmission structure, so that a mode'sintensity-energy peak in the analyte-affected output light has arespective light spot on a photosensing IC in detector 210. Therefore,the sensing results can include information about at least one ofposition and intensity of a light spot as shown and, accordingly, aboutthe respective mode's intensity-energy peak. If the output light fromthe cavity includes intensity-energy peaks for two or more modes, theirrespective light spots can be tracked separately as described below.

The photosensed quantities read out in box 304 can also be digitallyadjusted by CPU 240 before being stored for each object and mode, in box306. The digital adjustment can include adjusting quantities photosensedby cells based on reference quantities, and can also include anynecessary adjustments due to differences in sensing periods or otherfactors. The digital adjustment in box 306 and the analog adjustment, ifany, in box 304 can employ reference cell techniques described inco-pending U.S. patent application Ser. No. 11/316,438, entitled“Photosensing Throughout Energy Range and in Subranges” and incorporatedherein by reference in its entirety; such reference cell-basedadjustment techniques may be especially useful for intensity referencingin tracking an object's position, and can, in general, be performed inrelation both to measurements of refractive index and also ofabsorption. In particular, such adjustments can be used to overcomeproblems with inhomogeneous illumination, but such techniques may bedifficult to implement successfully in system 200 because externalinhomogeneities that affect output light, such as in illumination or instable or time-varying absorption by particles between light sources 220and optical cavity 204, are not readily distinguishable from absorptionwithin cavity 204. In other words, adjustment based on reference cellsmay remove desired information about absorption changes inside cavity204.

To avoid this and other such problems, the operation in box 306 or asubsequent operation can make an alternative data manipulation oradjustment to obtain “cavity-only absorption data”, an expression thatrefers herein to values or other data in which information aboutabsorption in cavity 204 is preserved while information is reduced aboutfeatures exterior to cavity 204 such as inhomogeneities in illuminationand external absorption, as described in co-pending U.S. patentapplication Ser. No. ______, [Attorney Docket No.20060251-US-NP/U1047/035], entitled “Obtaining Information From OpticalCavity Output Light” and incorporated herein by reference in itsentirety. As will be understood, the encoding of absorption informationin the manner described herein allows removal of noise-like effectsother than those from absorption coefficient inside cavity 204,influences such as external perturbations, disturbances, orinhomogeneities. As a result, measurements of absorption can have ahigher signal to noise ratio. Also, information can be recovered fromanalyte-encoded output light that is selectively sensitive to absorptionchanges inside cavity 204.

The position and speed information about each object from box 302 can beused by the operation in box 306 to determine which photosensedquantities result from effects of each object. Similar techniques can beused to determine which photosensed quantities result from each mode'slight spot when a cavity's output light includes two or more modes.

For homogeneous analyte in cavity 204 or for stationary or slow-movingobjects in cavity 204, lock-in techniques could be applied to furtherimprove signal to noise ratio, such as by modifying operations in boxes302, 304, and 306 in FIG. 9. For example, illumination from lightsources 220 can be modulated in order to modulate output light fromcavity 204. The applicable modulation frequencies would be constrainedby the readout frequency achievable by detector 210. In implementationswhere it is not possible to directly record a correlation signal,another type of reference could be used, such as an empty channel in afluidic structure, a channel with a reference medium, or an uncoatedreference cell in a photosensing array with coated cells to sense photonenergy subranges.

In performing the operations in boxes 304 and 306, CPU 240 can employdata structures (not shown) stored in memory 246. For example, one datastructure can store each object's previously calculated position andspeed, which can then be used in performing subsequent calculations toidentify effects of the same object; similarly, each object's datastructure can also include each light spot's identifying information andthe object's effect on the identified light spot, which can similarly beused in subsequent calculations. Also, a readout data structure can beemployed to hold all of the adjusted quantity information about eachobject.

The operation in box 306 can update the readout data structure each timeit obtains additional information about the same object. In animplementation as in FIG. 8, the operations in boxes 300, 302, 304, and306 can be performed separately for each of ICs 260 through 262.Further, as suggested by the dashed line from box 306 to box 300, thesame operations can be performed repeatedly for each of the ICs. If eachobject can be correctly identified throughout its travel along a paththrough cavity 204, the readout data structure can be used to hold allof the information obtained from all ICs. Between consecutive executionsof the operations in boxes 300, 302, 304, and 306, the effects of eachobject may move only a few cells along the path, and consecutive objectsmust be sufficiently separated to avoid confusion. For example, eachobject may be a few μm in diameter, each cell may have a length alongthe path of between 10 and 20 μm, and consecutive objects may be two orthree cell lengths apart. For larger objects or for cells of differentsizes, the spacing between consecutive objects can be adjustedappropriately.

Various modifications could be made in the implementation of FIG. 9. Forexample, rather than being spaced apart, objects could be closertogether. Even if several objects are having overlapping effects on alight spot, it may be possible to perform computational algorithms toseparate the effects of the objects. Similarly, if objects are veryclose to each other but positioned along different cells, an opticalstructure between the path of the objects and detector 210 could ensurethat photons affected by different objects travel to different cells; inthis way, a continuous stream of objects could be measured. Furthermore,techniques as described above could be applied to a continuous fluidicstream without distinguishable objects in it, in which case theanalyte-affected output light from optical cavity 204 would bedetermined by optical characteristics of concentrations of molecules ineach position in the stream rather than by optical characteristics ofdistinguishable objects. In effect, the stream would be divided intoimaginary small volumes, each of which would be an object analyzed asdescribed above, allowing for continuous monitoring of how the outputlight from the fluid changes with time, such as due to changingcomposition of the fluid.

As the operations in boxes 300, 302, 304, and 306 are repeated while anobject travels along a path past detector 210, more and more informationis obtained, especially where a cavity's output light has more than onelight spot, with each light spot having a respective position on thearray. When the object has passed the whole array, information about theanalyte it contains can be recomposed from the stored fractions.

Upon completion of any suitable amount of information gathering in boxes300, 302, 304, and 306, CPU 240 can perform the operation in box 310 toprovide analyte information, such as in the form of data for anotherroutine or as output through external I/O 249. As shown, this operationcan include combining the sensed quantities for each object so thatanalyte information for the object can be provided, such as in the formof an absorption spectrum, a value for the analyte's refractive index,or some other data structure.

FIG. 10 shows device 350, which could be used in an implementation ofsystem 200. Entry glass 352 and an exit glass (not shown) are ofsubstantially the same size and shape, and their inward-facing surfaceshave coatings or other structures that function as light-reflectivecomponents, reflecting light into a light-transmissive region betweenthem to operate as an optical cavity. The two glasses are illustrativelyseparated by spacers 354 and the light-transmissive region may alsocontain fluidic walls or other structures (not shown) that bound a ductor channel between inlet 356 and outlet 358; as a result, an analyte ora fluid carrying an analyte can enter the optical cavity from inlet 356,can be carried along a path through the optical cavity such as through aduct or channel, and can then exit from the optical cavity to outlet358.

Over or on entry glass 352 is light source component 360, which caninclude one or more light sources such as lasers, LEDs, or superluminescence diode (SLDs) to illuminate the optical cavity. Photosensingarray 362 is on the underside or below the exit glass, positioned alongthe analyte's path through the optical cavity. Light source component360, array 362, and the optical cavity between them have characteristicssuch that the optical cavity responds to illumination from the lightsources by providing analyte-affected output light that can bephotosensed by array 362.

FIG. 11 shows a longitudinal cross-section of device 350, viewed alongthe line 11-11 in FIG. 10. In the illustrated cross-section, lightsources 360 are providing light, represented by arrows 380, which passesthrough entry glass 352 and through entry light-reflective structure 382before entering channel 384. Within channel 384, a moving fluid such asa liquid, gas, or aerosol, represented by arrows 390, carries an object392. While object 392 is present in the optical cavity, its opticalcharacteristics can affect light reflected within channel 384 betweenentry light-reflective structure 382 and exit light-reflective structure394. As a result, analyte-affected output light exits through exitlight-reflective structure 394 and is transmitted through exit glass 396and then transmission structure 398 before being photosensed by array362.

In general, object 392 can be a particle, droplet, or small volume offluid that can be carried by a fluid or other appropriate substance andthat includes an analyte to be analyzed. The term “object” is usedherein in the general sense of any distinguishable thing that can haveoptical characteristics such as refractive index and absorption. Moregenerally, any energy shifting or loss mechanism associated with adistinguishable thing within the cavity affects transmitted andreflected wavelength and intensity, and is therefore a type of opticalcharacteristic as used herein, including, for example, scattering andreflection.

The terms “fluidic structure” and “channel” are used herein with relatedmeanings: A “fluidic structure” is a structure that depends for itsoperation on fluid positioning or fluid flow, such as, for liquids orgases, in response to pressure or, for liquids, as a result of surfacetension effects; a “channel” is any tube or other enclosed passagedefined within a fluidic structure and through which fluid flows duringoperation. The direction in which fluid flows within a channel issometimes referred to herein as a “flow direction.”

Transmission structure 398 can be an LVF implemented as described abovein relation to FIG. 4 or can be any other appropriate transmissionstructure with a suitable laterally varying energy output function, sothat incident light on array 362 similarly has a “laterally varyingphoton energy distribution” or simply a “laterally varying energydistribution”, meaning that photon energy of incident light varies as afunction of lateral position. For example, transmission structure 398can provide a laterally varying energy distribution on array 362 bytransmitting, at each position along channel 384, only light in arespective narrow subrange of photon energies, with the respectivesubranges being different at different positions along channel 384.Therefore, for each position, a respective set of one or more cells ofarray 362 receives light only if the position's respective subrangeincludes or overlaps with a subrange in which the optical cavity isproviding output light, such as the subrange of an intensity-energy peakas illustrated in FIG. 4.

A detector or other device or apparatus including both transmissionstructure 398 and array 362 could be implemented in a wide variety ofways, some of which are described in co-pending U.S. patent applicationSer. No. 11/315,386, entitled “Sensing Photon Energies Emanating fromChannels or Moving Objects,” and incorporated herein by reference in itsentirety. For example, array 362 could have a photosensitive surfacewith an appropriate pixel- or cell-density and transmission structure398 could be a coating over the photosensitive surface that operates asan LVF.

Array 362 could be implemented with any appropriate readout technique,such as CMOS or CCD readout, for which cell dimensions of 5-50 μm arecurrently typical, and smaller cell dimensions are foreseeable. Althougharray 362 could be a one-dimensional array with a line of cells parallelto the flow direction of arrows 390, implementation with atwo-dimensional array could beneficially provide, at each position alongthe path of object 392, a set of two or more cells in a lineperpendicular to the flow direction, with all the cells in the setconcurrently photosensing incident light in the same photon energysubrange; sensing results from each set of cells could be used toaverage or otherwise combine and improve information obtained for agiven transmission mode's output light.

Entry and exit light-reflective structures 382 and 394 operate as twoparallel mirrors, with channel 384 being a light-transmission regionbetween them, providing an optical cavity as described above. Withappropriate parameters, the cavity can operate as a Fabry-Perotinterferometer, and its transmission properties will be determined bythe mirrors and the region between them: The mirrors affect FWHM ofpeaks of the cavity's transmission spectrum and their reflectivity alsoaffects the quality of the stop-band, i.e. how much light is transmittedoutside of transmission modes. Also, the refractive index and distancebetween structures 382 and 394 affect or determine the photon energiesthat are transmitted by the optical cavity.

Each of structures 382 and 394 can be implemented as a layered structurewith alternating dielectric layers or with metal, deposited in eithercase on entry glass 352 and exit glass 396. Rather than glasses 352 and396, the enclosing walls of channel 384 through which light enters andexits could instead be implemented with any other suitablelight-transmissive components with inward-facing surfaces that are orcan be made reflective, such as by fabrication of appropriate structureson them.

In an illustrative implementation, light source 360 illuminates theoptical cavity homogeneously with a collimated light beam from asuitable light source, such as an LED, broadband laser, orsuperluminescence diode (SLD); suitable optical components can be usedto spread a light beam to illuminate all of array 362, such as withspreading components as disclosed in copending U.S. patent applicationSer. No. 11/315,387, entitled “Propagating Light to be Sensed” andincorporated herein by reference in its entirety. In otherimplementations, light source 360 could include or be replaced by anarray of light sources, reducing or eliminating the need for spreading.For example, a single broadband light source like an LED or SLD could bereplaced by an array of laser diodes (not shown) or narrow-band emittingLEDs (e.g. resonant cavity LEDs), each emitting at a respectivewavelength; this approach could beneficially increase the interactionlength between light and analyte in larger cavities in which interactionlength is limited by a light source's coherence length. In addition,since different positions of transmission structure 398 transmitdifferent photon energy subranges, each laser diode in the array couldbeneficially be positioned or oriented to illuminate a respectiveposition at which transmission structure 398 transmits the diode'semission wavelength.

If object 392 is absent and fluid in channel 384 is homogeneous, device350 can operate as a homogeneous optical cavity as described above inrelation to FIGS. 2 and 3. The output light from the optical cavity caninclude one or more discrete transmission modes if the dimensions andrefractive index of the optical cavity are appropriate. The presence ofobject 392, however, can change the refractive index and absorption ofthe optical cavity due to optical characteristics of object 392. Forexample, if object 392 has a certain absorption spectrum, it can affectthe intensity amplitude Imax and the FWHM of each transmitted mode asillustrated in FIG. 3 and also its contrast as described above;similarly, the refractive index of object 392 can affect photon energiesof the modes as illustrated in FIG. 3. These are examples of “encodinginformation” about optical characteristics, an expression used herein torefer to any operation or combination of operations by which an opticalcavity's output light is modified in a way that depends on opticalcharacteristics, such as of object 392.

In response to output light from the optical cavity, array 362 canaccordingly obtain sensing results that indicate changes in the centralenergy, intensity amplitude, contrast, and FWHM of each transmittedmode, providing information about object 392 and its effect on therefractive index and absorption in the optical cavity. The sensingresults can then be used, such as by CPU 240 in executing analyteinformation routine 274 to “obtain information”, an expression usedherein to refer to any operation or combination of operations performedon sensing results from photosensing an optical cavity's output lightand that produce indications of information encoded in the output light;the indications could, for example, be electrical signals, data storedby an appropriate memory device, displayed information, and so forth.For example, sensing results that indicate intensity, FWHM (or otherintermediate intensity width), contrast (e.g. Tmax/Tmin or othersuitable value), or any other relevant measurable feature of eachtransmitted mode can be used to obtain data indicating an absorptionvalue for a given photon energy such as the central wavelength of themode; similarly, sensing results indicating central energy shift can beused to obtain data indicating a refractive index value for the opticalcavity with object 392 present.

An alternative approach could encode information about opticalcharacteristics in reflection modes of a Fabry-Perot cavity rather thanin transmission modes. Sensing results from reflection modes could beused, for example, to obtain information about absorption spectra andrefractive index dispersion. This approach could be beneficial inapplications where improved readout sensitivity is desirable: Asdescribed above in relation to box 36 in FIG. 1, analyte could fill orotherwise be positioned within a slightly asymmetric Fabry-Perot cavitydesigned so that the cavity with analyte approximates a symmetricFabry-Perot cavity, which would be true for a cavity of width w andabsorption a if the second mirror's effective reflectivity Reff(2) issubstantially equal to the first mirror's reflectivity R(1) as follows:

Reff(2)=R(2)*exp(−2aw)=R(1)

In some implementations of system 200, object 392 would be a biologicalcell carried by liquid flowing through channel 384, and device 350 couldbe used to encode information about optical characteristics of a seriesof such cells and to obtain sensing results indicating the encodedinformation; information about the optical characteristics could then beobtained from the sensing results by CPU 240 and used in an appropriateway, such as for the purpose of distinguishing types of biologicalcells. In encoding and obtaining information about refractive index, forexample, the information will result not only from a biological cell butalso from the fluid or other medium that is carrying it and fillschannel 384 around the cell. The resulting measured refractive indexwill therefore be a combination between that of the fluid and that ofthe biological cell. If the size of the cell is known, its actualrefractive index could be determined from the measured refractive index;the size of the cell can be determined, for example, by using a Coultercounter and/or a light scattering unit, such as an MIE scatteringdevice.

FIG. 12 shows two transmission spectra that illustrate how a change inrefractive index shifts transmission peaks. The illustrated portion ofthe spectra includes six pairs of peaks near a wavelength of 1.0 μm. Ineach pair, the leftward peak was obtained with a refractive index of1.30 while the rightward peak was obtained with a refractive index of1.31. In both cases, the width w of the cavity operating as aFabry-Perot interferometer was 10 μm. As can be seen, the FSR isapproximately 37 nm, while the shift Δλ resulting from the refractiveindex change of 0.01 is approximately 8 nm. This is consistent with thefollowing equations for the case of incident light parallel to thereflection direction:

${FSR} = {{{\lambda (k)} - {\lambda \left( {k + 1} \right)}} = {{2{{nw}/{k\left( {k + 1} \right)}}}\overset{k->\infty}{\approx}{{\left( {\lambda (k)} \right)^{2}/2}{nw}}}}$and Δλ(k) = 2Δ nw/k.

In general, the first of these equations shows that FSR becomes smaller,and transmission peaks therefore become closer, as w increases. Also, aslight increase in n causes a slight increase in FSR. These effects,however, are not readily visible in FIG. 12.

In designing device 350 to encode information about optical absorptionand to obtain sensing results indicating such information, severalconstraints must be taken into account—the desired absorption orinteraction length; the desired volume of analyte; the required photonenergy range and resolution for absorption spectra; the wavelengthresolution of the detector that includes transmission structure 398 andarray 362; and so forth. To reach a suitable compromise between theseconstraints, several parameters can be adjusted, including the width ofthe cavity, the reflectivity of the mirrors, size of array 162,properties of transmission structure 398, and possibly absorption withinthe cavity, though absorption is not easily adjusted.

Device 350 as in FIGS. 10 and 11 can also be used to encode informationabout a homogeneous analyte such as a liquid, gas, or aerosol, withinchannel 384 without the presence of object 392. For example, a singlereadout of sensing results from array 362 can provide information aboutthe transmission spectrum of the homogeneous analyte. If the analytechanges on a relatively long time scale compared to transit time throughdevice 350, sensing results read out at different times can indicatelong-term changes of the transmission spectrum. For this approach,however, accurate measurements can only be obtained if the analytepresent within channel 384 during a given readout is substantiallyhomogeneous.

FIG. 13 illustrates graphically the effect an analyte can have on aFabry-Perot interferometer's transmission spectrum. The cavityillustratively has a width w of 75 μm and a mirror reflectivity of 95%.Without analyte present in the cavity, each of the illustratedtransmission modes transmits light to a normalized intensity amplitudeof 1.0, as shown in the upper part of FIG. 13.

With the analyte present, in this case glucose in water, transmission ofnearly all modes is decreased due to absorption, with the resultingpeaks for the illustrated modes falling on curve 410 in the lower partof FIG. 13. Curve 410 can therefore indicate the absorption spectrum ofthe analyte, with the circles 412 serving as discrete sampling points ofthe absorption spectrum. In order to measure the absorption spectrum toa desired resolution, the cavity width w and other parameters must bechosen to obtain a sufficient number of sampling points.

FIG. 13 also suggests that increased glucose absorption dramaticallyreduces intensity of a mode because of the strongly enhanced interactionlength that occurs within a cavity with highly reflective mirrors. Thismeans that light bounces back and forth within the cavity many timesbefore being transmitted. As described above, the increased analyteabsorption also causes broadening of the modes. The larger theabsorption, the smaller the mode's intensity and contrast and the largerthe mode's FWHM (or other intermediate intensity width); the lower partof FIG. 13 does not fully show the change in FWHM that would occur.Additional details about effects of absorption are provided inco-pending U.S. patent application Ser. No. ______ [Attorney Docket No.20051733Q-US-NP/U1047/041], entitled “Encoding Optical Cavity OutputLight” and incorporated herein by reference in its entirety.

As suggested by arrows 390 in FIG. 11, object 392 can move at arelatively uniform speed along a path within channel 384. As a result,its effect on transmission modes of the optical cavity will also followa path, allowing correlation between sensing results from array 362 andthe position of object 392, such as with the techniques described inco-pending U.S. patent application Ser. No. 11/315,386, entitled“Sensing Photon Energies Emanating from Channels or Moving Objects” andincorporated herein by reference in its entirety. In effect, a series ofcells in array 362 obtain sensing results that include information aboutoptical characteristics of object 392. These sensing results can be usedto obtain information as described herein.

In the specific example illustrated in FIG. 11, absorption spectroscopycould be performed, for example, by obtaining sensing results as object392 moves through channel 384, using the sensing results to obtainactual absorption values of object 392 for each transmission mode basedon biological cell size and flow velocity, and composing an absorptionspectrum using the actual values obtained. This technique takesadvantage of the motion of object 392 for improved detection, and alsoenables large integration times without losing throughput capacity.Highly sensitive optical absorption spectroscopy can be performed inthis manner.

FIGS. 14-15 show device 440, an alternative implementation with featuressimilar to those shown in FIGS. 10-11, but with multiple channels 450,452, 454, 456, and 458 bounded by walls 460 and with a flow directionindicated by arrows 462. A single two-dimensional photosensing array 470can obtain sensing results for all the channels, with sets of cellsproviding sensing results in the manner described above fortwo-dimensional arrays. Biological cells or other objects, representedby the shaded circles such as circle 472, can be correlated with theirsensing results based on flow velocity, as described above.

FIG. 15 shows a cross-section of device 440 taken along the line 15-15in FIG. 14. As in FIG. 11 above, light sources 480 could be implementedin any appropriate way to illuminate channels 450 through 458. Entryglass 482 could have entry light-reflective component 484 formed on itsinward-facing surface as described above, and exit glass 494 (or anothersubstrate that can carry a mirror) could have exit light-reflectivecomponent 492 formed on its inward-facing surface. Transmissionstructure 490 could be formed on array 470.

Transmission structure 490 could be implemented in any of severaldifferent ways to provide desired sensing results. For example,transmission structure 490 could be a layered structure, implementedwith any of the techniques described in co-pending U.S. patentapplication Ser. No. 11/316,303, entitled “Obtaining AnalyteInformation” and incorporated herein by reference in its entirety.

In one exemplary implementation, transmission structure 490 could be anLVF that is graded in the x-direction shown in FIG. 14 but ishomogeneous in the y-direction. In this case, array 470 would besensitive to the same photon energy subrange in all of channels 450through 458. Therefore, information about the same changes in refractiveindices and absorption information could be obtained from all thechannels, with parallel positions in the channels providing informationabout the same photon energy subranges. Since the subranges vary alongeach channel, information can be obtained for a number of differentsubranges or for an entire spectrum as a biological cell or other objectis carried through a channel. In this case, all channels are identicaland objects or analytes are characterized in the same manner independentof the channel through which they are passing.

In another exemplary implementation, transmission structure 490 could bean LVF that is graded in the y-direction in FIG. 14 but homogeneous inthe x-direction. This arrangement could be obtained, for example, byrotating the previously described exemplary implementation through 90°.In this case, a set of two or more cells that extend in a line across achannel at a certain position will receive different photon energysubranges, so that the intensity ratio between cells in such a set willchange as a biological cell or other object passes by while beingcarried through the channel. In this case, refractive index change of anobject can be recorded as a function of time while it is moving alongthe channel, or multiple measurements or longer integration times (inthe case of a homogeneous analyte) can be used to increase sensitivity.Note that in parallel channels different modes are used to determinerefractive index.

In yet another exemplary implementation, transmission structure 490could be graded in both the x-direction and the y-direction. This casewould allow information to be obtained about different subranges in bothof the ways described above.

In general, various referencing techniques could be used to measureoptical characteristics such as absorption spectra and refractive indexvalues by comparison to reference values obtained from the same opticalcavity, such as with a known reference solution or other fluid. In theimplementation in FIGS. 14 and 15, for example, every other channel,such as channels 452 and 456, could serve as a reference channel if itis empty or contains only a known homogeneous reference fluid, allowingmore precise evaluation of absorption spectra and dispersion of therefractive index in channels 450, 454, and 458, such as by comparingmeasured analyte values with measured reference values; for example, tosense glucose concentration based on optical characteristics, thereference medium could be a known glucose concentration. Since referencemedium and analyte are moving within the same environment or channelsystem this also allows compensation for external influences (liketemperature, pressure, etc.) that may have a significant influence onoptical properties.

FIG. 16 illustrates exemplary operations in producing a device likedevice 350 in FIGS. 10 and 11 or device 440 in FIGS. 14 and 15. Inparticular, the operations in FIG. 16 make it possible to produceapparatus in which information about optical characteristics of ananalyte can be encoded and sensing results indicating the informationabout the optical characteristics can be obtained.

The operation in box 520 in FIG. 16 produces entry and exit partialoptical cavity structures. This operation can include producing entrylight-reflective structure 382 on entry glass 352 and also producingexit light-reflective structure 394 on exit glass 396, both as in FIG.11. Similarly, this operation can include producing entrylight-reflective component 484 on entry glass 482 and also producingtransmission structure 490 and exit light-reflective light component 492on photosensing array 470 as in FIG. 15. This operation can also includeproducing a patterned layer of SU-8 or polydimethylsiloxane (PDMS) onone or both of the light-reflective structures, such as with techniquesdescribed in co-pending U.S. patent application Ser. No. 11/315,992,entitled “Sensing Photons from Objects in Channels” and incorporatedherein by reference in its entirety. This patterned layer could includestructures such as spacers 354 in FIG. 10 and walls 460 in FIGS. 14 and15. If appropriate, an anti-adhesive coating can be applied to interiorchannel surfaces, such as by dip-coating polyethylene glycol (PEG) or byproviding a coating of parylene C or vapor deposited tetraglyme.

The operation in box 522 then attaches the entry and exit partialstructures, with attached fluidic components to position analyte in theresulting optical cavity. The operation in box 522 can include forming asuitable bond between the entry and exit partial structures so that theyare firmly attached to each other. Also, the fluidic components attachedto the resulting optical cavity structure can include, for example,connectors, tubing, pumps, sensors, and so forth; it is important thatthe combination of fluidic components be capable of operating to causeand control positioning of analyte within the optical cavity, such as bycarrying the analyte into the optical cavity with a fluid or in someother way. The operation in box 522 can also optionally includeattachment of wires or other appropriate circuitry connected, forexample, to the photosensing array.

The operation in box 524 then attaches any other additional componentsnecessary to complete the device. For example, if the device includeslight sources, such as light source component 360 in FIGS. 10 and 11 orlight sources 480 in FIG. 15, these components can be attached by theoperation in box 524. Similarly, if a detector that includes aphotosensing array and a transmission structure is not part of the exitpartial structure, as in FIG. 15, the detector can be attached by theoperation in box 524. The operation in box 524 can also include anyother external electrical, optical, or fluidic connections necessary foroperation of the device. Alternatively, such connections could later bemade when the device is incorporated into a system, such as system 200in FIGS. 7 and 8.

The operation in box 526 can be performed at any appropriate time afterthe other operations, as suggested by the dashed line from box 524 tobox 526. In addition, the operation in box 526 performs calibration,which requires that components be appropriately connected to circuitry,such as in the ways illustrated in FIGS. 7 and 8. The necessaryconnections could be created as part of the operations in boxes 520,522, and 524 or instead could be created after the operation in box 524and before performing calibration. In any case, calibration in box 526can include obtaining items of data or data structures to be used inobtaining analyte information as described herein, and the data or datastructures can be stored in memory 246 as part of calibration data 276(FIG. 8), or, in appropriate cases, can be embedded in analyteinformation routine 274 or stored in another appropriate form.

In general, the operations in any of boxes 520, 522, 524, and 526 caninclude additional activities. For example, at any appropriate point inproduction of the device, wires or other appropriate circuitry can beattached to provide signals to or from a microprocessor or input/output(I/O) device to pumps and other fluidic components or to provide signalsfrom a photosensing array to a microprocessor or I/O device. Similarly,connections can be made at any appropriate time to provide power.

The technique of FIG. 16 could be modified in many ways within the scopeof the invention. For example, the operations in boxes 520, 522, and 524could be combined in any appropriate way to facilitate attachment ofcomponents in a desired sequence. Also, an additional operation could beperformed to align or attach interconnects between ICs, gates, and othercircuitry, such as connectors to a microprocessor or computer, or thisoperation could be partially performed in each of boxes 520, 522, 524,and 526. Furthermore, the technique of FIG. 16 is extremely general, andcould be employed to produce a wide variety of different devices thatencode information about optical characteristics of analyte within anoptical cavity and obtain sensing results indicating the opticalcharacteristics. The examples illustrated in FIGS. 10, 11, 14, and 15above show how objects can be carried through a channel within anoptical cavity while such operations are performed, but various otherarrangements are possible, some examples of which are described below.

FIG. 17 illustrates a different type of implementation in which relativemovement between analyte and photosensing array occurs, but in a mannerdifferent from the implementation in FIGS. 14 and 15. Photosensing array550 moves relative to a biochip with an array of wells each of which cancontain analyte or another fluid, such as a reference fluid; each wellis represented in FIG. 17 by a shaded circle, such as circle 552.Relative motion between array 550 and the biochip is indicated by arrow554. The biochip can, for example, be sandwiched between two mirrors(not shown) so that each well is within the optical cavity formedbetween the mirrors, and the cavity can be illuminated in any of variousways; the illustrated technique makes it unnecessary to perform scanningillumination, since illumination and sensing can be fully parallel. Inthe case, for example, in which the biochip is moved in the x-directionas indicated by arrow 554 and in which a transmission structure (notshown) over array 550 is an LVF with a gradient in the x-direction buthomogeneous in the y-direction, each of the wells can pass along arespective path across the array along which sensing results areobtained for each photon energy subrange of a spectrum, allowing forstep-by-step spectral characterization of the contents of each well. Thewells can be correlated with their respective sensing results based onthe relative velocity, similarly to the techniques described above.After all sensing results are obtained, a deconvolution of the sensingresults can be performed to obtain the absorption spectrum andrefractive index dispersion for each well of the biochip.

The techniques illustrated in FIGS. 14, 15, and 17 are only a few of themany possible ways of implementing relative motion between analyte in anoptical cavity and a photosensing component. Additional techniques aredescribed in co-pending U.S. patent application Ser. No. ______[Attorney Docket No. 20051733Q2-US-NP/U1047/043], entitled “MovingAnalytes and Photosensors” and incorporated herein by reference in itsentirety.

FIG. 18 shows setup 600, a combination of components that can be used ina system as in FIGS. 7 and 8, but possibly without an optical cavitystructure as defined above; instead, a combination of components couldoperate as a laser cavity even though they may not be connected into astructure. Laser mirrors 602 and 604 provide reflection surfaces for thelaser cavity, and gain medium 606 provides laser amplification. Duct610, shown in dashed lines, represents a path along which objects can becarried through the laser cavity, with objects 612, 614, and 616illustratively being carried in the direction indicated by arrows 618;objects 612, 614, and 616 could, for example, be small volumes of fluid,biological cells, or any other type of particle or object as describedabove.

As a result of the presence of any of objects 612, 614, and 616 in thelaser cavity, emitted light represented by arrows 620 includesinformation about optical characteristics of analyte. Possibly after aspreading operation as described in co-pending U.S. patent applicationSer. No. 11/315,387, entitled “Propagating Light to be Sensed” andincorporated herein by reference in its entirety, the analyte-affectedoutput light is transmitted through transmission structure 622, whichcan be an LVF, and is photosensed by photosensing array 624. Setup 600therefore makes it possible to obtain information, for example, aboutrefractive index of objects 612, 614, and 616, because a change inrefractive index in the laser cavity causes a shift of the emitted laserwavelength, in the manner described by Liang X. J., Liu, A. Q., Zhang,X. M., Yap, P. H., Ayi, T. C., and Yoon, H. S., “Refractive IndexMeasurement of Single Living Cell Using a Biophotonic Chip for CancerDiagnosis Applications,” 9^(th) International Conference on MiniaturizedSystems for Chemistry and Life Sciences, Oct. 9-13, 2005, Boston, Mass.,2005, pp. 464-466.

Setup 600 can be implemented, for example, with an external cavity laserdiode. A detector that includes transmission structure 622 and array 624can be implemented in any of the ways described above to obtain aninexpensive, compact structure that can very precisely and rapidly sensethe shift of emitted laser wavelength resulting from refractive indexchange. By simultaneously monitoring the intensity of the laser output,analyte-induced cavity loss, such as absorption at the laser wavelength,can be recorded.

FIG. 19 shows device 650, which can also be used in a system as in FIGS.7 and 8. Light-reflective structures 652 and 654 provide reflectionsurfaces on either side of region 656, which can be filled with analyteas shown. As a result, when input light, represented by arrows 658, isreceived through structure 652, optical cavity operation can occur,resulting in transmission of light to photosensing component 660. Theindex of refraction of analyte in region 656 and the positioning ofstructures 652 and 654 determine positions of light transmission, andillumination can be provided so that only certain wavelengths aretransmitted, one of which is represented by arrow 662.

FIG. 20 shows an example of the pattern of light on the upper surface ofphotosensing component 660 if the optical cavity were illuminated inonly one narrow wavelength band. As shown, light spot 664 onphotosensing component 660 indicates that the incident narrow band lightis transmitted at a certain position Xtrans. If analyte refractive indexchanges, the location of the transmitted light spot 364 would move,either toward Xmin or Xmax. If analyte absorption changes, causing achange in intensity and FWHM of output light's intensity function, thesize and intensity of light spot 364 would change.

Inhomogeneous optical cavities that contain analyte can be implementedin many ways in addition to the way illustrated in FIGS. 19 and 20.Additional techniques are described in co-pending U.S. patentapplication Ser. No. ______ [Attorney Docket No.20061188-US-NP/U1047/044], entitled “Containing Analyte In OpticalCavity Structures” and incorporated herein by reference in its entirety.In many applications, an optical cavity structure as in FIGS. 1 and 7could be implemented to include one or more inhomogeneous opticalcavities that contain analyte as in FIGS. 19-20. Furthermore, theoptical cavity in device 650 could instead be a homogeneous opticalcavity that contains analyte and that is operated to provide a laterallyvarying output energy distribution, by providing a range of angles atwhich input light is incident, as described in co-pending U.S. patentapplication Ser. No. 11/316,438, entitled “Photosensing ThroughoutEnergy Range and in Subranges” and incorporated herein by reference inits entirety.

FIG. 21 shows device 680, which can also be used in a system as in FIGS.7 and 8, such as to produce an inhomogeneous optical cavity as in FIG.19 or to produce a tunable homogeneous or inhomogeneous cavity,including cavities through which objects can travel. Light-reflectivestructures 682 and 684, together with the region between them, canoperate as an optical cavity when illuminated by input light,represented by arrows 686.

Structures 682 and 684 have electrodes 690 on their inward surfaces,facing each other and with elastically deformable spacers 692 and 694,such as elastomer or other deformable material between them. As aresult, signals can be provided to electrodes 690 to cause changes indistances between structures 682 and 684, changing the shape of theregion between them, as suggested by angle 696. At positions wherephoton energy of input light is the same as a transmission mode ofdevice 680, light is transmitted to photosensing component 698, whichobtains sensing results. If analyte is present in the region betweenstructures 682 and 684, optical cavity operation can provideanalyte-affected output light. By independently addressing theelectrodes on different spacers, it is also possible to keep atransmission mode's position unchanged while a neighboring mode movesfurther away or outside of the area of a photosensing device. Thissuggests how sensitivity and wavelength band can be chosenindependently.

FIG. 22 illustrates an example of how device 680 can be adjusted toobtain two different transmission spectra. The intensity-energy graph inFIG. 22 includes two curves: The curve that includes peaks 710 resultsfrom a spacing of 4.8 microns between structures 682 and 684, while thecurve that includes peaks 712 results from a spacing of 5 microns.Although these curves indicate operation of device 680 as a homogeneousoptical cavity, similar results would occur if it were operated as aninhomogeneous cavity as illustrated in FIG. 21, though anintensity-position graph would be more appropriate in that case. Ineither case, the output light could include information about opticalcharacteristics of analyte in the region between structures 682 and 684,encoded as described above in relation to FIGS. 3 and 5.

Adjustments as in FIG. 22 can be performed at different intervals withdevice 680 to vary the absorption sampling points as in FIG. 13. Forgreater resolution of an absorption spectrum, for example, the number ofsampling points can be increased, and it is in principle possible tocontinuously vary the thickness or tilt to obtain a continuous spectrum.Furthermore, a derivative, such as of absorption, can be directlymeasured by recording mode intensity while continuously changing cavitythickness; sensitivity of this technique can be further increased if thethickness is periodically modulated with a small amplitude (wobble)during the continuous change of cavity thickness.

The techniques in FIGS. 21 and 22 can also be extended to obtainderivatives by calculating slope between measurements of absorption orother optical characteristics at pairs of incrementally different photonenergies obtained by tuning a homogeneous optical cavity that containsanalyte. Similarly, cavity shape can be adjusted by such techniques toimprove sensitivity.

A device as in FIG. 21 can also be used for other purposes, such as toproduce an optical cavity or transmission structure with desiredcharacteristics. For example, a homogeneous or inhomogeneous opticalcavity with desired optical thickness could be produced; similarly, atransmission structure that is an LVF with a desired gradient could beproduced.

Tunable cavities that can be inhomogeneous or that can contain analytecould be implemented in many ways besides the way illustrated inrelation to FIGS. 21 and 22. Additional techniques are described, forexample, in co-pending U.S. patent application Ser. No. ______ [AttorneyDocket No. 20061409-US-NP/U1047/045], entitled “Tuning Optical Cavities”and in co-pending U.S. patent application Ser. No. ______ [AttorneyDocket No. 20061409Q-US-NP/U1047/046], entitled “Tuning OpticalCavities”, both of which are incorporated by reference herein in theirentireties. In general, an optical cavity structure as in FIGS. 1 and 7could be implemented to include one or more tunable cavities as in FIGS.19-20.

FIG. 23 illustrates an application of a system as in FIGS. 7 and 8 inanalyzer 750 on support structure 752, a fluidic structure. Defined insupport structure 752 is serpentine channel 754 through which object 756can travel, carried by a fluid or other appropriate substance. Object756 can, for example, be a droplet or a small volume of fluid thatincludes an analyte to be analyzed.

The manner in which object 756 enters channel 754 and is carried byfluid can be the same as described in co-pending U.S. patent applicationSer. No. 11/315,386, entitled “Sensing Photon Energies Emanating fromChannels or Moving Objects” and incorporated herein by reference in itsentirety. As explained there, object 756 can be carried through channel754 by operation of propulsion components and can be purged or otherwisecaused to exit, together with fluid that is carrying it, from one ofseveral outlets, such as through toggling of valves. While in channel754, object 756 can travel through a series of sensing components, eachof which can obtain information about object 756.

The first two sensing components after object 756 enters channel 754 areillustratively Coulter counter 760, an electrically based particle sizedetector, and Mie scatter sensor 762, also a particle size detector. Asmentioned above, information about size of object 756 can be used inobtaining information about its optical characteristics, and thisinformation can be obtained from Coulter counter 760 and Mie scattersensor 762.

The next sensing component along channel 754 is optical cavity sensor770, shown schematically in a cross-sectional view similar to that ofFIG. 11, although it would typically be implemented instead withcomponents above and below channel 754, similarly to other sensingcomponents described below. The schematic illustration of sensor 770includes light-reflective components 772 and 774 and detector 776, allof which might be implemented in a variety of ways, including some ofthose described above. In addition, one or more light sources (notshown) could illuminate the optical cavity.

After passing through sensor 770, particle 756 can continue throughsubsequent sensing components, illustratively including components 782and 784. These could, for example, include first and second fluorescencesensing components and a Raman scatter sensing component. Informationobtained from any combination of the sensing components can be used todistinguish types of objects, such as different types of biologicalcells. Based on such a distinction, valve 790 at a bifurcation junctioncan be toggled between two positions, with object 756 exiting asindicating by arrow 792 if valve 790 is in one position and exiting asindicated by arrow 794 if value 790 is in another position. Examples ofways in which objects can be distinguished are described in greaterdetail in co-pending U.S. patent application Ser. No. ______ [AttorneyDocket No. 20051733Q1-US-NP/U1047/042], entitled “DistinguishingObjects” and incorporated herein by reference in its entirety.

FIG. 24 illustrates another application of a system as described abovein relation to FIGS. 7 and 8. System 800 illustratively includes threecomponents, various combinations of which could be feasibly implemented.Optical cavity component 802 receives input light from light sourcecomponent 804 and, in turn, provides its output light to detectorcomponent 806. In the illustrated example, optical cavity component 802is shown in cross-sectional view, showing how light-reflectivestructures 810 and 812 and wall structures 814 and 816 define tworegions between light-reflective structures 810 and 812. Region 820,bounded by structures 810, 812, 814, and 816, can contain a referencefluid, while region 822, also bounded by structures 810, 812, and 816but open at a side opposite wall structure 816, can contain fluid thatenters as indicated by arrow 824.

In operation, analyte-carrying fluid, such as blood, lymph, interstitialfluid from between the cells of a human's or other organism's body, orother bodily fluid, can enter region 822 through any appropriatephysical process; the analyte can be glucose, for example. As a result,optical cavity component 802 in effect operates as two parallel opticalcavities: One optical cavity includes region 820 and provides outputlight, represented by arrow 830, with information about opticalcharacteristics of the reference fluid (e.g. interstitial fluid with awell-known concentration); the other optical cavity includes region 822and provides output light, represented by arrow 832, with informationabout a sample of fluid in which the analyte may be present. Detector806 obtains sensing results that include both types of information andthe sensing results can be provided to an external component such as aCPU or other processor, as indicated by arrow 834.

System 800 could be implemented in many different ways, and can includevarious optical cavity components, light sources, and detectors,including some of those described above. In addition to wristwatch-likeimplementations in which interstitial fluid is brought to the skinsurface through small tubes or pins and then positioned in region 822,such as in one of the ways described above in relation to FIG. 1,several other implementations of system 800 using implantable productsare described in co-pending U.S. patent application Ser. No. ______[Attorney Docket No. 20060271-US-NP/U1047/036], entitled “ImplantingOptical Cavity Structures” and incorporated herein by reference in itsentirety.

FIGS. 25-33 illustrate ways in which information about opticalcharacteristics can be encoded in and obtained from output light from anoptical cavity, such as in system 200 in FIGS. 7 and 8, in system 800 inFIG. 24, or in any of the other implementations described above. Thetechniques described in relation to FIGS. 25-33 are, however, merelyillustrative, and various other techniques could be used for encodinginformation in an optical cavity's output light and then obtaininginformation from the output light, with or without intermediateoperations on the output light such as transmission, reflection,focusing, spreading, filtering, or other forms of propagation or opticalprocessing. Furthermore, the information encoded and obtained in thetechniques of FIGS. 25-33 generally relates to optical characteristicsof analytes, but information about other types of opticalcharacteristics or other types of information in general could beencoded in and obtained from output light from optical cavities usingtechniques described herein.

FIGS. 25 and 26 illustrate one of the ways in which information aboutrefractive index can be encoded and also suggest how information can inturn be obtained from photosensed quantities read out from aphotosensing array. The transmission spectra, each with severalintensity-energy peaks for respective transmission modes, were obtainedby simulating a cavity similar to that described above in relation toFIG. 12, first with a refractive index n=1.30 for FIG. 25 and then witha refractive index n=1.29 for FIG. 26. Estimated intensity-energysensing spectra of four illustrative cells of a photosensing array werethen combined with the resulting transmission spectra, so that eachfigure shows how the intensity-energy transmission spectrum of thecavity at a respective refractive index overlaps with theintensity-energy sensing spectra of the cells.

FIG. 25 shows how sensing peak 900 overlaps very well with atransmission peak at approximately 965 nm, sensing peaks 902 and 904 donot overlap well with any of the transmission peaks, and sensing peak906 overlaps almost perfectly with a transmission peak at 1000 nm. Then,after a change of refractive index, FIG. 26 shows that sensing peaks900, 902, and 906 do not overlap very well with any of the transmissionpeaks, while sensing peak 904 now overlaps almost perfectly with atransmission peak at approximately 990 nm.

As noted above, a change in refractive index can be encoded as a shiftin photon energy of a cavity's transmission or reflection modes. FIGS.25 and 26 suggest several ways in which this encoded information cansubsequently be obtained from the cavity's output light: If it is known,for example, that refractive index has one of a number of discretevalues, an appropriate threshold quantity can be compared with thephotosensed quantity of each cell to obtain one binary value for eachcell, and these binary values would often correspond with refractiveindices; in the example in FIGS. 25 and 26, a threshold could be usedthat would provide a binary value of 1001 for a refractive index of 1.30and a value of 0010 for a refractive index of 1.29, with each binaryvalue in effect indicating the extent of overlap between each of sensingpeaks 900, 902, 904, and 906 with transmission peaks. Alternatively, adifferential quantity could be obtained indicating a shift of wavelengthin one or more of the transmission peaks, such as with the techniquesdescribed in co-pending U.S. patent application Ser. No. ______[Attorney Docket No. 20040195-US-CIP/U1047/038], entitled“Position-Based Response to Light” and incorporated herein by referencein its entirety; a differential quantity obtained, for example, betweenthe cells with sensing peaks 904 and 906 could indicate a shift betweenrefractive indices, and differential values obtained between other pairsof cells could indicate other such shifts. In general, in these andother similar techniques, an increase in the number of cells increasesthe amount of information obtained, allowing for redundancy that can beused for averaging and a higher confidence level.

FIGS. 27 and 28 illustrate encoding of information about absorption inan optical cavity like that described above in relation to FIG. 13. Ineach figure, three transmission peaks are shown at wavelengths ofapproximately 2.216 μm, 2.242 μm, and 2.268 μm. In FIG. 27, intensity ofthe peaks, normalized to overall maximum intensity Imax, is shown on alogarithmic scale, but in FIG. 28, intensity is only normalized to eachpeak's maximum intensity Imax (peak), which brings out the relationshipsbetween the FWHMs of the peaks.

As can be seen from FIG. 27, transmitted intensity decreases by abouttwo orders of magnitude as absorption increases from zero to 60 per cm,with the highest peak in FIG. 27 being obtained for an absorption ofzero, the lowest being obtained for an absorption of 120 per cm, and thesecond from the lowest being for 60 per cm. The increasing FWHM due toabsorption is shown in FIG. 28 in which the order is reversed, with theupper curve being that for 120 per cm and the lowest curve being forzero absorption. As can be seen, FWHM approximately doubles ifabsorption doubles, such as between the second curve from the top, for60 per cm, and the top curve, for 120 per cm.

The curves in FIGS. 27 and 28 can be related to ordinary analytes suchas air and water. A density of zero corresponds, for example, with theabsorption of air, so that the top peak in FIG. 27 and the lowest curvein FIG. 28 indicate the effect of no absorption when the optical cavityis filled with air. Water, on the other hand, has an absorption ofapproximately 30 per cm at wavelengths around 2.2 μm, so that the secondpeak from the top in FIG. 27 and the second lowest curve in FIG. 28indicate absorption in an optical cavity filled with water.

The effect of an analyte in a fluidic or aerosol chamber within an airor water filled cavity can be analyzed mathematically. In general, theproblem is to determine how small absorption changes will be encoded inthe cavity's output light.

The transmittance T_(FP) of a Fabry-Perot optical cavity with incidentlight perpendicular to its entry surface is given by:

${T_{FP} = \frac{T\; \max}{1 + \left( {\frac{2F}{\pi}\sin \; \delta} \right)^{2}}},{where}$${\delta = \frac{2\pi \; {nw}}{\lambda}},$

the finesse F is given by:

${F = \frac{\pi \sqrt{\sqrt{R\; 1R\; 2}^{{- \alpha}\; w}}}{1 - {\left( \sqrt{R\; 1R\; 2} \right)^{{- \alpha}\; w}}}},$

and the maximum transmittance Tmax is given by:

${{T\; \max} = \frac{\left( {1 - {R\; 1}} \right)\left( {1 - {R\; 2}} \right)^{{- \alpha}\; w}}{\left( {1 - {\left( \sqrt{R\; 1R\; 2} \right)^{{- \alpha}\; w}}} \right)^{2}}},$

with R1 and R2 being the reflectivities of the two mirrors and a beingthe absorption coefficient of the medium within the cavity.

FIG. 29 shows relative change in transmittance ΔT/T as a function ofabsorption a for several different reflectivities ranging from zero forthe uppermost line to 0.999 for the lowermost and most steeply slopedline. The plotted values were obtained from the equation:

$\frac{\Delta \; T}{T} = {\frac{\left( {{T\; {\max \left( {\alpha = 0} \right)}} - {T\; {\max (\alpha)}}} \right)}{T\; {\max \left( {\alpha = 0} \right)}}.}$

The plotted values were obtained with a width w of 10 μm and arefractive index n=1.3. In effect, the uppermost line represents aconventional absorption measurement without an optical cavity(reflectivity of both mirrors is zero), while the magnitude of ΔT/Tincreases as reflectivity increases, causing the line with the greatestreflectivity to have the steepest slope. This is consistent with theparticle theory of light under which increasing reflectivity leads tomore reflections of each photon before it exits from the cavity, so thatits interaction length with the analyte is extended.

An enhancement factor E indicating the increase in interaction lengthcan be obtained from the following equation:

$E = {\frac{\frac{\Delta \; T}{T}(R)}{\frac{\Delta \; T}{T}\left( {R = 0} \right)}.}$

The enhancement factor E therefore compares the interaction length of aFabry-Perot cavity with a conventional absorption measuring setup havingzero reflectivity.

FIG. 30 is a graph showing the enhancement factor E for the same cavityas in FIG. 29 and with the same reflectivities, again plotted as afunction of absorption a in an air-filled Fabry-Perot cavity. The lowestline in FIG. 30 indicates the enhancement factor E for reflectivity ofzero, while the uppermost line indicates the enhancement factor E forreflectivity of 0.999. As can be seen, the enhancement factor Eincreases dramatically with reflectivity but remains substantiallyconstant for a given reflectivity despite absorption changes.

FIGS. 31 and 32 are the same as FIGS. 29 and 30, but obtained for thecase in which the cavity is filled with water. As a result, in FIG. 31,the negative slope of ΔT/T does not increase as rapidly with increasingreflectivity, and, in FIG. 32, the enhancement factor E similarly doesnot increase as rapidly with increasing reflectivity, and also decreasesslightly as absorption increases across the illustrated range, at leastfor higher reflectivities.

FIG. 33 illustrates the relationship between photosensing array 920 andcurves 922, 924, and 926, each of which is a normalized intensityfunction of a transmission mode in output light from a Fabry-Perotcavity. As will be understood, the result illustrated in FIG. 33 can beobtained, for example, by providing output light with anintensity-energy function having a peak, passing the output lightthrough an LVF or other transmission structure with a laterally varyingtransmission function, and receiving the resulting laterally varyingenergy distribution on the photosensitive surface that includes thecells of array 920.

Each of curves 922, 924, and 926 is a peak with approximately the samecentral energy, but the intermediate intensity width (e.g. FWHM) narrowsfrom peak 922 to peak 924 and again from peak 924 to peak 926.Therefore, the number of cells of array 920 that receive intensity abovea given dynamic threshold (e.g. 50% of the maximum peak intensity) willbe greater for curve 922 than for curve 924, and will similarly begreater for curve 924 than for curve 926.

As can be seen from FIG. 33, the number of cells with photosensedquantities above a defined threshold provides a measure of intermediateintensity width (e.g. FWHM) of a given mode. FIG. 33 also illustrateshow cell density provides a lower limit on FWHM resolution. Becausecurve 926 provides above-threshold intensity for only one or perhaps twocells of array 920, its FWHM will be poorly resolved. In other words,the density of cells of array 920 is insufficient to resolve curve 926from similar curves with slightly different FWHMs, as could otherwise bedone by obtaining a Gaussian or Lorentzian fit of each curve betweenminima. In general, the resolution of array 920 must be sufficient thatthe narrowest peak obtained during normal operating conditions providesabove-threshold photosensed quantities to more than one cell of array920, as suggested in FIG. 33. In many applications, it is moreconvenient to use another referencing technique, such as sensing orcalculating contrast-based data or another, non-width type ofcavity-only absorption data, to determine absorption or absorptionchanges within the cavity, as described above in relation to box 306 inFIG. 9, rather than to determine FWHM or another intermediate intensitywidth.

As noted above in relation to FIG. 23, it is possible to integrateseveral analysis tools onto a single detection platform to collectinformation about an analyte, including sensing components forabsorption, fluorescence, Raman spectroscopy, pH, and Coulter counters.It is similarly possible, and can be advantageous, to combine techniquesthat encode and obtain information about refractive index withtechniques that encode and obtain information about optical absorption.Techniques as described above can perform both types of encoding andobtaining of information, with the result that changes in refractiveindex result in changed central energy of a cavity's modes, whilechanges in absorption spectrum cause changes in amplitude and FWHM ofthe cavity's modes. The relationship between refractive index andabsorption follows from the definition of the complex refractive indexñ=n+iκ, where n is the refractive index and κ is the extinctioncoefficient. The extinction coefficient κ is related to the absorptioncoefficient α as follows:

$\alpha = {\frac{4{\pi\kappa}}{\lambda}.}$

Although absorption and refractive index are related to each other bythe Kramers-Kronig relation, they are not really redundant. In otherwords, additional information can be obtained by measuring both, since,for example, a calculation of refractive index change requiresinformation about absorption change over a very broad spectral range.Since usual measurements are made across limited spectral ranges inwhich refractive index changes might be strongly influenced byabsorption changes in another spectral range, it is advantageous tomeasure both quantities separately. In particular, it is possible toobtain information about very small refractive index changes, whichcould not be obtained merely by measuring absorption changes.

The techniques described above also allow measurement of dispersion ofrefractive index, based on measurement of refractive index at each of acavity's modes. In other words, dispersion can be obtained by measuringthe shift of each mode's central energy separately.

In summary, measuring small analyte-induced refractive index changes anddispersion of refractive index can provide additional information aboutthe analyte beyond what is available from measurement of absorptionalone. Therefore, it can be advantageous to encode and obtaininformation about both absorption and refractive index dispersionconcurrently for a desired photon energy range, and this can be donewith a single system implemented as described above.

Techniques as described above also make it possible to measure localderivatives of refractive index and absorption, such as in anextinction-energy curve in which extinction K is measured as a functionof wavelength across a desired range of photon energies. The derivativeof the absorption spectrum is an independent and powerful item ofinformation that can be used to distinguish analytes; it can be used,for example, to distinguish glucose from other interstitial fluidmolecules such as alanine, ascorbate, BSA, lactate, triacetin, and urea.A number of such molecules strongly influence the absorption spectrumwithin a wavelength band of interest for glucose, such as 2.5-2.40 μm.The derivative of the absorption spectrum of glucose, however, providesan even more characteristic differentiator from the other molecules thanthe absorption spectrum itself.

Glucose is an example, however, in which measurement can become morecomplicated. A change of glucose concentration can also changeabsorption at a respective narrow photon energy subrange; also, aglucose-induced absorption change that occurs throughout a broaderphoton energy range can correlate with a small refractive index changethat slightly shifts central energy of a Fabry-Perot cavity's mode underthe Kramers-Kronig relation. The transmitted intensity of the shiftedmode is therefore affected both by (1) increasing or decreasingabsorption and also by (2) shift to a photon energy with higher or lowerintensity. Either of effects (1) and (2) can dominate, depending on thespectral position of the mode within the absorption spectrum of glucose:Effect (1) dominates at a maximum, minimum, or plateau of the absorptionspectrum where dα/dλ is zero; effect (2) dominates in regions of largechange within the absorption spectrum, where abs (dα/dλ)>>0, because themode's intensity function is changing mainly due to refractiveindex-induced spectral shift to a region of higher or lower absorption.A detected intensity change can therefore be an indication of absorptionwhere effect (1) dominates or an indication of derivative of absorptionwhere effect (2) dominates.

The implementations in FIGS. 1-33 illustrate various applications oftechniques as described above, including positioning analyte in anoptical cavity and operating the cavity to provide analyte-encodedoutput light, such as with information about the analyte's refractiveindex and absorption coefficient.

Techniques that encode information about analytes, as exemplified by theimplementations in FIGS. 1-33, can be applied in many biochip andlab-on-chip devices and in micro total analysis systems, in which acompact unit able to measure optical characteristics of analytes withhigh accuracy would be highly desirable. Information about refractiveindex and absorption, for example, could be valuable in controlling afabrication process or a chemical reaction, for example; the controlledchemical reaction could possibly occur inside the optical cavity,allowing measurement of refractive indices and absorption coefficientseven of transitory analytes resulting from the reaction. Refractiveindex and/or absorption index could be criteria used to make processcontrol decisions, or could be used in a multivariable analysis,including one or more other types of information such as fluorescence orimpedance.

Refractive index and absorption might be especially valuable forbiological and biomedical applications. For example, the techniquesdescribed above could be used to measure optical properties (refractiveindex, dispersion, scattering and absorption values) of single livingcells in real time without extra treatment. Similarly, the techniquescould be used to measure absorption coefficient and derivative to detectglucose or other analytes in bodily fluids, such as by using animplantable product. The techniques could also be implemented in asophisticated fluidic system, as in flow cytometry and cell sortingsystems, to count, sort, separate, select, or otherwise distinguishliving cells of different types that are in a medium. For example,cancerous and non-cancerous cells could be counted and/or sorted.

The techniques could be applied not only to read out biochips or as partof a complex analysis system with fluidic or aerosol channels, but alsoin various other applications. They can be used, for example, in fluidicsample sensing, gas sensing, aerosol sensing, and so forth.

Various of the techniques described above have been successfullyimplemented or simulated, including the production and operation of ahighly sensitive detector that includes a commercially available ICcovered with a laterally graded Fabry-Perot cavity filter on a glassslide, and that can detect, for example, wavelength shift. Changes oflaser and Fabry-Perot mode intensity peaks to indicate analyte opticalcharacteristics have been simulated.

The exemplary implementations described above allow compact, inexpensivecomponents to rapidly and accurately perform operations such asmeasuring optical characteristics of fluids, biological cells, glucose,and other analytes. In general, the techniques can be implemented inexisting sensors and photosensors.

The exemplary implementations described above employ optical cavitieswith specific parameters and modes, but a wide variety of cavities couldbe used. Cavities with widths in the range from a few μm to hundreds ofμm are feasible, and photon energies ranging from the ultraviolet up tothe far infrared could be sampled.

In addition, components could have various shapes, dimensions, or othernumerical or qualitative characteristics other than those illustratedand described above. For example, in some exemplary implementationsdescribed above, cells of a photosensor array photosense in differentsubranges of an application's photon energy range. The subranges ofcells could have any appropriate widths and relationships, and could,for example, overlap or be distinct. The width of a cell's subrange canbe chosen by designing the transmission structure and the cell sensingarea; for example, the width may be as small as 0.1 nm or as great astens of nanometers.

Some of the above exemplary implementations involve specific materials,such as in optical cavities and their components, but the inventioncould be implemented with a wide variety of materials and with layeredstructures with various combinations of sublayers.

Similarly, optical cavities could be fabricated with any appropriatetechniques, including thin film technology such as sputtering, e-beam orthermal evaporation with or without plasma assistance, epitaxial growth,MBE, MOCVD, and so forth. To produce Bragg mirrors, appropriate pairs ofmaterials with low absorption coefficients and large difference inrefractive indices could be chosen, bearing in mind the photon energiesof interest; exemplary materials include SiO₂/TiO₂, SiO₂/Ta₂O₅,GaAs/AlAs, and GaAs/AlGaAs. Thicknesses of layer in transmissionstructures may vary from 30 nm up to a few hundred nanometers.

Some of the above exemplary implementations could involve particulartypes of optical cavities, such as Bragg mirrors and paired distributedBragg reflectors separated by a Fabry-Perot cavity, but, more generally,any appropriate optical cavity could be used to encode analyte opticalcharacteristics. Various techniques could be used to produce opticalcavities in addition to those described above, including, duringdeposition, tilting the substrate, using a shadow mask, or using atemperature gradient to obtain graded layer thickness; also, duringhomogeneous deposition, off-axis doping, such as by e-beam, MBE, orMOVPE, could produce lateral variation.

Some of the above exemplary implementations use specific lasers or otherlight sources to obtain light with desired characteristics, but variousother light source techniques could be used within the scope of theinvention. Various propagation components that propagate light betweenother components could also be employed.

The exemplary implementation in FIGS. 8 and 9 employs a CPU, which couldbe a microprocessor or any other appropriate component. Furthermore, asnoted above, adjustment, combining, and other operations on photosensedquantities could be done either digitally or with analog signals, andcould be done either on the same IC as a photosensor array, on othercomponents, or on a combination of the two, with any appropriatecombination of software or hardware.

The above exemplary implementations generally involve production and/oruse of optical cavities, light sources, analyte positioning components;optical cavity operating components; processing circuitry, and controlcircuitry following particular operations, but different operationscould be performed, the order of the operations could be modified, andadditional operations could be added within the scope of the invention.Also, readout of adjusted or unadjusted photosensed quantities from anIC could be performed serially or in parallel, and could be performedcell-by-cell or in a streaming operation.

While the invention has been described in conjunction with specificexemplary implementations, it is evident to those skilled in the artthat many alternatives, modifications, and variations will be apparentin light of the foregoing description. Accordingly, the invention isintended to embrace all other such alternatives, modifications, andvariations that fall within the spirit and scope of the appended claims.

1. A method of using an optical cavity that is operable to provideoutput light in one or more modes; when providing output light in one ofthe modes with analyte absent, the optical cavity providing the outputlight with a respective unencoded intensity function; the methodcomprising: positioning an analyte in the optical cavity, the analytehaving a respective optical characteristic; and while the analyte ispositioned in the optical cavity, providing analyte-affected outputlight in at least one of the modes; the analyte-affected output lightfrom each mode having a respective encoded intensity function that isdifferent than its unencoded intensity function; the differenceindicating the analyte's optical characteristic.
 2. The method of claim1, further comprising: photosensing the output light to obtain sensingresults that depend on intensity function; and using the sensing resultsto obtain information about the analyte's optical characteristic.
 3. Themethod of claim 1 in which the optical cavity is a Fabry-Perot cavity.4. The method of claim 1 in which the cavity is an inhomogeneous opticalcavity.
 5. The method of claim 1 in which the analyte's opticalcharacteristic includes at least one of a refraction characteristic andan absorption characteristic.
 6. The method of claim 1 in which theunencoded and encoded intensity functions each have a respective centralvalue and in which the analyte's optical characteristic includes arefraction characteristic; the unencoded and encoded central valueshaving a difference that indicates the refraction characteristic.
 7. Themethod of claim 1 in which the unencoded and encoded intensity functionseach have a respective maximum intensity or contrast and in which theanalyte's optical characteristic includes an absorption characteristic;the unencoded and encoded maximum intensities or contrasts having adifference that indicates the absorption characteristic.
 8. The methodof claim 1 in which the unencoded and encoded intensity-energy functionseach have a respective intermediate intensity width and in which theanalyte's optical characteristic includes an absorption characteristic;the unencoded and encoded intermediate intensity widths having adifference that indicates the absorption characteristic.
 9. The methodof claim 8 in which each intermediate intensity width is a full widthhalf maximum (FWHM).
 10. The method of claim 1 in which the analyte'soptical characteristic includes both a refraction characteristic and anabsorption characteristic.
 11. The method of claim 1 in which the act ofpositioning the analyte comprises: moving the analyte along a fluidicchannel extending through the cavity.
 12. The method of claim 1 in whichthe modes include at least one of transmission modes and reflectionmodes, the method further comprising: illuminating the cavity so that itprovides output light in only one mode.
 13. The method of claim 1 inwhich the modes include at least one of transmission modes andreflection modes, the method further comprising: illuminating the cavityso that it provides output light in two or more modes.
 14. A systemcomprising: an analyte positioning component that can position ananalyte in an optical cavity, the optical cavity being operable toprovide output light in one or more modes; when providing output lightin one of the modes with analyte absent, the optical cavity providingthe output light with a respective unencoded intensity function; theanalyte having a respective optical characteristic; and an opticalcavity operating component that, while the analyte is positioned in theoptical cavity, can operate the optical cavity to providinganalyte-affected output light in at least one of the modes; theanalyte-affected output light from each mode having a respective encodedintensity function that is different than its unencoded intensityfunction; the difference indicating the analyte's opticalcharacteristic.
 15. The system of claim 14, further comprising controlcircuitry that provides signals to control the analyte positioningcomponent and the optical cavity operating component.
 16. The system ofclaim 14, further comprising: an optical cavity structure that includesfirst and second light-reflective components and a light-transmissiveregion between them, the light-reflective components andlight-transmissive region being operable as the optical cavity; theoptical cavity structure including an opening within thelight-transmissive region; the analyte positioning componenttransferring analyte into the opening.
 17. The system of claim 16 inwhich the optical cavity is asymmetric when analyte is not in theopening and approximately symmetric when analyte is in the opening. 18.The system of claim 16 in which the opening is a well in a side of abiochip, the first light-reflective component being on a side of thebiochip opposite the well; the analyte positioning component furtheroperating to cover the well with the second light-reflective component.19. The system of claim 14, further comprising: an optical cavitystructure that includes two light-reflective components and alight-transmissive region between them, the light-reflective componentsand light-transmissive region being operable as the optical cavity; theoptical cavity structure including a set of one or more channelsextending through the light-transmissive region; the analyte positioningcomponent transferring analyte through the light-transmissive region inthe channels.
 20. The system of claim 19 in which the set includes twoor more channels.
 21. The system of claim 19 in which the analyte iscarried through the light-transmissive region by a fluid.
 22. The systemof claim 21 in which the analyte is a fluid that travels through thelight-transmissive region in one or more of the channels in the set. 23.The system of claim 19 in which the channel travels through thelight-transmissive region by traveling through a medium in one or moreof the channels in the set.
 24. A method of using an optical cavity thatis operable to provide output light in one or more modes; when providingoutput light in one of the modes with analyte absent, the optical cavityproviding the output light with a respective unencoded intensityfunction; the method comprising: positioning each of a sequence of twoor more analytes in the optical cavity, each analyte in the sequencehaving a respective optical characteristic, the optical characteristicsof analytes varying within the sequence; and while each analyte ispositioned in the cavity, operating the optical cavity so that itprovides respective analyte-affected output light in each of a subset ofthe modes, the respective analyte-affected output light of at least onemode in the subset having an intensity function that varies as a resultof the varying optical characteristics of the analytes.
 25. The methodof claim 24 in which each analyte is in a respective object; the act ofpositioning comprising: moving each of a sequence of the analyte'srespective objects through the optical cavity.
 26. A device comprising:a Fabry-Perot cavity that is operable to provide output light in one ormore of a set of transmission modes; the cavity having an analyte regiontherein in which analyte can be positioned; with analyte absent from theanalyte region, the Fabry-Perot cavity being optically asymmetric; withanalyte present in the analyte region, the Fabry-Perot cavity beingoptically symmetric; when operating in at least one mode in the set withanalyte present in the analyte region, the Fabry-Perot cavity providingoutput light with a respective intensity function that, depends on anoptical characteristic of the analyte moving each of a sequence of theanalyte's respective objects through the optical cavity.
 27. The deviceof claim 26, further comprising an optical cavity structure thatincludes the Fabry-Perot cavity; the Fabry-Perot cavity being one of alaser and a transmissive cavity.
 28. The device of claim 26 in which theFabry-Perot cavity provides output light in a mode with the mode'srespective intensity functions having a respective intensity peak.